Adenovirus E3 Proteins
Apoptosis Regulatory Proteins
Apoptosis
Caspases
RNA-Binding Proteins
Cell Death
Molecular Sequence Data
Cause of Death
Amino Acid Sequence
bcl-Associated Death Protein
Death
Death, Sudden, Cardiac
Proto-Oncogene Proteins c-bcl-2
Brain Death
Attitude to Death
Genes, bcl-2
Cell Survival
Proto-Oncogene Proteins
Signal Transduction
bcl-2-Associated X Protein
Receptors, Death Domain
CARD Signaling Adaptor Proteins
Lymphoma, B-Cell
Caspase 3
Translocation, Genetic
Risk Factors
Chromosomes, Human, Pair 14
Mitochondria
Subcellular distribution and redistribution of Bcl-2 family proteins in human leukemia cells undergoing apoptosis. (1/660)
It has been suggested that the ratio of Bcl-2 family proapoptotic proteins to antiapoptotic proteins determines the sensitivity of leukemic cells to apoptosis. However, it is believed that Bcl-2 family proteins exert their function on apoptosis only when they target to the mitochondrial outer membrane. The vinblastine-resistant T-lymphoblastic leukemic cell line CEM/VLB100 has increased sensitivity to tumor necrosis factor-alpha (TNF-alpha)-induced cytochrome c release, mitochondrial respiratory inhibition, and consequently apoptosis, compared with parental CEM cells. However, there was no difference between the two cell lines in the expression of Bcl-2 family proteins Bcl-2, Bcl-XL, Bcl-XS, Bad, and Bax at the whole cell level, as analyzed by Western blotting. Bcl-2 mainly located to mitochondria and light membrane as a membrane-bound protein, whereas Bcl-XL was located in both mitochondria and cytosol. Similar levels of both Bcl-2 and Bcl-XL were present in the resting mitochondria of the two cell lines. Although the proapoptotic proteins Bcl-XS, Bad, and Bax were mainly located in the cytosol, CEM/VLB100 mitochondria expressed higher levels of these proapoptotic proteins. Subcellular redistribution of the Bcl-2 family proteins was detected in a cell-free system by both Western blotting and flow cytometry after exposure to TNF-alpha. The levels of Bcl-2 family proteins were not altered at the whole cell level by TNF-alpha. However, after exposure to TNF-alpha, Bax, Bad, and Bcl-XS translocated from the cytosol to the mitochondria of both cell lines. An increase in Bcl-2 levels was observed in CEM mitochondria, which showed resistance to TNF-alpha-induced cytochrome c release. By contrast, decreased mitochondrial Bcl-2 was observed in CEM/VLB100 cells, which released cytochrome c from the mitochondria and underwent apoptosis as detected by fluorescence microscopy. We conclude that mitochondrial levels of Bcl-2 family proteins may determine the sensitivity of leukemic cells to apoptosis and that, furthermore, these levels may change rapidly after exposure of cells to toxic stimuli. (+info)Dissociation of apoptosis from proliferation, protein kinase B activation, and BAD phosphorylation in interleukin-3-mediated phosphoinositide 3-kinase signaling. (2/660)
Interleukin-3 (IL-3) acts as both a growth and survival factor for many hemopoietic cells. IL-3 treatment of responsive cells leads to the rapid and transient activation of Class IA phosphoinositide-3-kinases (PI3Ks) and the serine/threonine kinase Akt/protein kinase B (PKB) and phosphorylation of BAD. Each of these molecules has been implicated in anti-apoptotic signaling in a wide range of cells. Using regulated expression of dominant-negative p85 (Deltap85) in stably transfected IL-3-dependent BaF/3 cells, we have specifically investigated the role of class IA PI3K in IL-3 signaling. The major functional consequence of Deltap85 expression in these cells is a highly reproducible, dramatic reduction in IL-3-induced proliferation. Expression of Deltap85 reduces IL-3-induced PKB phosphorylation and activation and phosphorylation of BAD dramatically, to levels seen in unstimulated cells. Despite these reductions, the levels of apoptosis observed in the same cells are very low and do not account for the reduction in IL-3-dependent proliferation we observe. These results show that Deltap85 inhibits both PKB activity and BAD phosphorylation without significantly affecting levels of apoptosis, suggesting that there are targets other than PKB and BAD that can transmit survival signals in these cells. Our data indicate that the prime target for PI3K action in IL-3 signaling is at the level of regulation of proliferation. (+info)Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD. (3/660)
The Ca2+-activated protein phosphatase calcineurin induces apoptosis, but the mechanism is unknown. Calcineurin was found to dephosphorylate BAD, a pro-apoptotic member of the Bcl-2 family, thus enhancing BAD heterodimerization with Bcl-xL and promoting apoptosis. The Ca2+-induced dephosphorylation of BAD correlated with its dissociation from 14-3-3 in the cytosol and translocation to mitochondria where Bcl-xL resides. In hippocampal neurons, L-glutamate, an inducer of Ca2+ influx and calcineurin activation, triggered mitochondrial targeting of BAD and apoptosis, which were both suppressible by coexpression of a dominant-inhibitory mutant of calcineurin or pharmacological inhibitors of this phosphatase. Thus, a Ca2+-inducible mechanism for apoptosis induction operates by regulating BAD phosphorylation and localization in cells. (+info)Trophic support promotes survival of bcl-x-deficient telencephalic cells in vitro. (4/660)
Survival of immature neurons is regulated by Bcl-xL, as targeted disruption of bcl-x significantly increases cell death in vivo and in vitro. Death of cultured bcl-x-deficient and wild-type telencephalic cells can be prevented by fetal calf serum or chemically-defined medium (ITS), suggesting trophic factors in these media potentiate survival through a pathway independent of Bcl-xL. Addition of trophic factors to basal medium revealed that insulin and insulin-like growth factors (IGFs), but not other trophic factors, reduced apoptosis of wild-type and bcl-x-deficient telencephalic cells. Antibodies raised against IGF-I receptors and wortmannin both attenuated the effects of IGF-I, indicating survival was mediated by IGF-I receptors and phosphatidylinositol 3'-kinase signaling, whereas effects of ITS were only partially reduced by these agents. The survival promoting effects of ITS were reduced in cells lacking both bcl-x and bcl-2, indicating Bcl-2 plays a supportive role to Bcl-xL in maintaining telencephalic cell survival. Furthermore, the ratio of expression of the pro-apoptotic bax gene to the anti-apoptotic bcl-2 gene was reduced in bcl-x-deficient cultures grown in ITS, suggesting that the interaction between these bcl-2 family members may, in part, regulate a Bcl-xL independent survival pathway. Finally, the pro-apoptotic bad gene does not appear to play a role in these interactions as targeted disruption of bad did not alter apoptosis in telencephalic cultures. (+info)Phosphorylation and inactivation of BAD by mitochondria-anchored protein kinase A. (5/660)
Signaling pathways between cell surface receptors and the BCL-2 family of proteins regulate cell death. Survival factors induce the phosphorylation and inactivation of BAD, a proapoptotic member. Purification of BAD kinase(s) identified membrane-based cAMP-dependent protein kinase (PKA) as a BAD Ser-112 (S112) site-specific kinase. PKA-specific inhibitors blocked the IL-3-induced phosphorylation on S112 of endogenous BAD as well as mitochondria-based BAD S112 kinase activity. A blocking peptide that disrupts type II PKA holoenzyme association with A-kinase-anchoring proteins (AKAPs) also inhibited BAD phosphorylation and eliminated the BAD S112 kinase activity at mitochondria. Thus, the anchoring of PKA to mitochondria represents a focused subcellular kinase/substrate interaction that inactivates BAD at its target organelle in response to a survival factor. (+info)Developmental regulation of Bcl-2 family protein expression in the involuting mammary gland. (6/660)
Epithelial cells within the mammary gland undergo developmental programmes of proliferation and apoptosis during the pregnancy cycle. After weaning, secretory epithelial cells are removed by apoptosis. To determine whether members of the Bcl-2 gene family could be involved in regulating this process, we have examined whether changes in their expression occur during this developmental apoptotic program in vivo. Bax and Bcl-x were evenly expressed throughout development. However, expression of Bak and Bad was increased during late pregnancy and lactation, and the proteins were present during the time of maximal apoptotic involution. Thereafter, their levels declined. In contrast, Bcl-w was expressed in pregnancy and lactation but was downregulated at the onset of apoptosis. Bcl-2 was not detected in lactating or early involuting mammary gland. Thus, the pro-apoptotic proteins Bax, Bak and Bad, as well as the death-suppressors Bcl-x, Bcl-2 and Bcl-w, are synthesised in mouse mammary gland, and dynamic changes in the expression profiles of these proteins occurs during development. To determine if changes in Bak and Bcl-w expression could regulate mammary apoptosis, their effect on cultured mouse mammary epithelial cells was examined in transient transfection assays. Enforced expression of Bak induced rapid mammary apoptosis, which could be suppressed by coexpression of Bcl-w. In extracts of mammary tissue in vivo, Bak heterodimerized with Bcl-x whereas Bax associated with Bcl-w, but Bak/Bcl-w heterodimers were not detected. Thus, Bak and Bcl-w may regulate cell death through independent pathways. These results support a model in which mammary epithelial cells are primed for apoptosis during the transition from pregnancy to lactation by de novo expression of the death effectors Bak and Bad. It is suggested that these proteins are prevented from triggering apoptosis by anti-apoptotic Bcl-2 family proteins until involution, when the levels of Bcl-w decline. Our study provides evidence that regulated changes in the expression of cell death genes may contribute to the developmental control of mammary apoptosis. (+info)Phosphorylation of the transcription factor forkhead family member FKHR by protein kinase B. (7/660)
Protein kinase B lies "downstream" of phosphatidylinositide (PtdIns) 3-kinase and is thought to mediate many of the intracellular actions of insulin and other growth factors. Here we show that FKHR, a human homologue of the DAF16 transcription factor in Caenorhabditis elegans, is rapidly phosphorylated by human protein kinase Balpha (PKBalpha) at Thr-24, Ser-256, and Ser-319 in vitro and at a much faster rate than BAD, which is thought to be a physiological substrate for PKB. The same three sites, which all lie in the canonical PKB consensus sequences (Arg-Xaa-Arg-Xaa-Xaa-(Ser/Thr)), became phosphorylated when FKHR was cotransfected with either PKB or PDK1 (an upstream activator of PKB). All three residues became phosphorylated when 293 cells were stimulated with insulin-like growth factor 1 (IGF-1). The IGF-1-induced phosphorylation was abolished by the PtdIns 3-kinase inhibitor wortmannin but not by PD 98059 (an inhibitor of the mitogen-activated protein kinase cascade) or by rapamycin. These results indicate that FKHR is a physiological substrate of PKB and that it may mediate some of the physiological effects of PKB on gene expression. DAF16 is known to be a component of a signaling pathway that has been partially dissected genetically and includes homologues of the insulin/IGF-1 receptor, PtdIns 3-kinase and PKB. The conservation of Thr-24, Ser-256, and Ser-319 and the sequences surrounding them in DAF16 therefore suggests that DAF16 is also a direct substrate for PKB in C. elegans. (+info)Cytokine-induced protein kinase B activation and Bad phosphorylation do not correlate with cell survival of hemopoietic cells. (8/660)
Activation of phosphoinositide-3 kinases (PI3Ks), their downstream target protein kinase B (PKB), and phosphorylation of Bad have all been implicated in survival signaling in many systems. However, it is not known whether these events are sufficient or necessary to universally prevent apoptosis. To address this issue, we have used three different factor-dependent hemopoietic cell lines, MC/9, BaF/3, and factor-dependent (FD)-6, which respond to a range of cytokines, to investigate the relationship between PI3K, PKB, and Bad activity with survival. The cytokines IL-3, IL-4, stem cell factor (SCF), GM-CSF, and insulin all induced the rapid and transient activation of PKB in responsive cell lines. In all cases, cytokine-induced PKB activation was sensitive to inhibition by the PI3K inhibitor, LY294002. However, dual phosphorylation of the proapoptotic protein Bad was found not to correlate with PKB activation. In addition, we observed cell-type-specific differences in the ability of the same cytokine to induce Bad phosphorylation. Whereas IL-4 induced low levels of dual phosphorylation of Bad in FD-6, it was unable to in MC/9 or BaF/3. Insulin, which was the most potent inducer of PKB in FD-6, induced barely detectable Bad phosphorylation. In addition, the ability of a particular cytokine to induce PKB activity did not correlate with its ability to promote cell survival and/or proliferation. These data demonstrate that, in hemopoietic cells, activation of PKB does not automatically confer a survival signal or result in phosphorylation of Bad, implying that other survival pathways must be involved. (+info)Adenoviruses are a group of viruses that commonly cause respiratory infections, conjunctivitis, and gastroenteritis. The E3 region of the adenovirus genome encodes several proteins that play important roles in the virus's life cycle and its interactions with the host cell.
The E3 proteins include:
1. E3-10.4K: This protein helps to prevent the infected cell from undergoing programmed cell death (apoptosis), allowing the virus to continue replicating.
2. E3-14.7K: This protein inhibits the host cell's antiviral response by blocking the activation of certain immune signaling pathways.
3. E3-14.5K: This protein helps to prevent the infected cell from presenting viral antigens on its surface, which would otherwise alert the immune system to the infection.
4. E3-19K: This protein helps to stabilize the virion and protect it from being broken down by host cell enzymes.
5. E3-gp19K: This protein is involved in the transport of newly synthesized viral proteins to the endoplasmic reticulum, where they can be assembled into new virions.
6. E3-RID: This protein helps to protect the virus from being neutralized by antibodies produced by the host's immune system.
Overall, the E3 proteins play important roles in helping the adenovirus evade the host's immune response and establish a successful infection.
Apoptosis regulatory proteins are a group of proteins that play an essential role in the regulation and execution of apoptosis, also known as programmed cell death. This process is a normal part of development and tissue homeostasis, allowing for the elimination of damaged or unnecessary cells. The balance between pro-apoptotic and anti-apoptotic proteins determines whether a cell will undergo apoptosis.
Pro-apoptotic proteins, such as BAX, BID, and PUMA, promote apoptosis by neutralizing or counteracting the effects of anti-apoptotic proteins or by directly activating the apoptotic pathway. These proteins can be activated in response to various stimuli, including DNA damage, oxidative stress, and activation of the death receptor pathway.
Anti-apoptotic proteins, such as BCL-2, BCL-XL, and MCL-1, inhibit apoptosis by binding and neutralizing pro-apoptotic proteins or by preventing the release of cytochrome c from the mitochondria, which is a key step in the intrinsic apoptotic pathway.
Dysregulation of apoptosis regulatory proteins has been implicated in various diseases, including cancer, neurodegenerative disorders, and autoimmune diseases. Therefore, understanding the role of these proteins in apoptosis regulation is crucial for developing new therapeutic strategies to treat these conditions.
Apoptosis is a programmed and controlled cell death process that occurs in multicellular organisms. It is a natural process that helps maintain tissue homeostasis by eliminating damaged, infected, or unwanted cells. During apoptosis, the cell undergoes a series of morphological changes, including cell shrinkage, chromatin condensation, and fragmentation into membrane-bound vesicles called apoptotic bodies. These bodies are then recognized and engulfed by neighboring cells or phagocytic cells, preventing an inflammatory response. Apoptosis is regulated by a complex network of intracellular signaling pathways that involve proteins such as caspases, Bcl-2 family members, and inhibitors of apoptosis (IAPs).
Caspases are a family of protease enzymes that play essential roles in programmed cell death, also known as apoptosis. These enzymes are produced as inactive precursors and are activated when cells receive signals to undergo apoptosis. Once activated, caspases cleave specific protein substrates, leading to the characteristic morphological changes and DNA fragmentation associated with apoptotic cell death. Caspases also play roles in other cellular processes, including inflammation and differentiation. There are two types of caspases: initiator caspases (caspase-2, -8, -9, and -10) and effector caspases (caspase-3, -6, and -7). Initiator caspases are activated in response to various apoptotic signals and then activate the effector caspases, which carry out the proteolytic cleavage of cellular proteins. Dysregulation of caspase activity has been implicated in a variety of diseases, including neurodegenerative disorders, ischemic injury, and cancer.
RNA-binding proteins (RBPs) are a class of proteins that selectively interact with RNA molecules to form ribonucleoprotein complexes. These proteins play crucial roles in the post-transcriptional regulation of gene expression, including pre-mRNA processing, mRNA stability, transport, localization, and translation. RBPs recognize specific RNA sequences or structures through their modular RNA-binding domains, which can be highly degenerate and allow for the recognition of a wide range of RNA targets. The interaction between RBPs and RNA is often dynamic and can be regulated by various post-translational modifications of the proteins or by environmental stimuli, allowing for fine-tuning of gene expression in response to changing cellular needs. Dysregulation of RBP function has been implicated in various human diseases, including neurological disorders and cancer.
Cell death is the process by which cells cease to function and eventually die. There are several ways that cells can die, but the two most well-known and well-studied forms of cell death are apoptosis and necrosis.
Apoptosis is a programmed form of cell death that occurs as a normal and necessary process in the development and maintenance of healthy tissues. During apoptosis, the cell's DNA is broken down into small fragments, the cell shrinks, and the membrane around the cell becomes fragmented, allowing the cell to be easily removed by phagocytic cells without causing an inflammatory response.
Necrosis, on the other hand, is a form of cell death that occurs as a result of acute tissue injury or overwhelming stress. During necrosis, the cell's membrane becomes damaged and the contents of the cell are released into the surrounding tissue, causing an inflammatory response.
There are also other forms of cell death, such as autophagy, which is a process by which cells break down their own organelles and proteins to recycle nutrients and maintain energy homeostasis, and pyroptosis, which is a form of programmed cell death that occurs in response to infection and involves the activation of inflammatory caspases.
Cell death is an important process in many physiological and pathological processes, including development, tissue homeostasis, and disease. Dysregulation of cell death can contribute to the development of various diseases, including cancer, neurodegenerative disorders, and autoimmune diseases.
Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.
The "cause of death" is a medical determination of the disease, injury, or event that directly results in a person's death. This information is typically documented on a death certificate and may be used for public health surveillance, research, and legal purposes. The cause of death is usually determined by a physician based on their clinical judgment and any available medical evidence, such as laboratory test results, autopsy findings, or eyewitness accounts. In some cases, the cause of death may be uncertain or unknown, and the death may be classified as "natural," "accidental," "homicide," or "suicide" based on the available information.
An amino acid sequence is the specific order of amino acids in a protein or peptide molecule, formed by the linking of the amino group (-NH2) of one amino acid to the carboxyl group (-COOH) of another amino acid through a peptide bond. The sequence is determined by the genetic code and is unique to each type of protein or peptide. It plays a crucial role in determining the three-dimensional structure and function of proteins.
BCL-associated death protein, often referred to as BAD, is a type of protein that belongs to the BCL-2 family. These proteins play a crucial role in regulating programmed cell death, also known as apoptosis. Specifically, BAD is a pro-apoptotic protein, meaning it promotes cell death under certain conditions.
The function of BAD is tightly regulated through various post-translational modifications and interactions with other BCL-2 family members. When activated, BAD can bind to and inhibit anti-apoptotic proteins like BCL-2 or BCL-XL, thereby releasing pro-apoptotic proteins such as BAX and BAK, which form pores in the mitochondrial membrane and initiate the apoptotic cascade.
Dysregulation of BAD and other BCL-2 family members has been implicated in several diseases, including cancer and neurodegenerative disorders. For instance, overexpression of anti-apoptotic proteins or downregulation of pro-apoptotic proteins like BAD can contribute to tumor development and resistance to chemotherapy. Therefore, understanding the role of BAD and other BCL-2 family members in apoptosis regulation is essential for developing novel therapeutic strategies in cancer and other diseases.
Death is the cessation of all biological functions that sustain a living organism. It is characterized by the loss of brainstem reflexes, unresponsiveness, and apnea (no breathing). In medical terms, death can be defined as:
1. Cardiopulmonary Death: The irreversible cessation of circulatory and respiratory functions.
2. Brain Death: The irreversible loss of all brain function, including the brainstem. This is often used as a definition of death when performing organ donation.
It's important to note that the exact definition of death can vary somewhat based on cultural, religious, and legal perspectives.
Sudden cardiac death (SCD) is a sudden, unexpected natural death caused by the cessation of cardiac activity. It is often caused by cardiac arrhythmias, particularly ventricular fibrillation, and is often associated with underlying heart disease, although it can occur in people with no known heart condition. SCD is typically defined as a natural death due to cardiac causes that occurs within one hour of the onset of symptoms, or if the individual was last seen alive in a normal state of health, it can be defined as occurring within 24 hours.
It's important to note that sudden cardiac arrest (SCA) is different from SCD, although they are related. SCA refers to the sudden cessation of cardiac activity, which if not treated immediately can lead to SCD.
Proto-oncogene proteins c-bcl-2 are a group of proteins that play a role in regulating cell death (apoptosis). The c-bcl-2 gene produces one of these proteins, which helps to prevent cells from undergoing apoptosis. This protein is located on the membrane of mitochondria and endoplasmic reticulum and it can inhibit the release of cytochrome c, a key player in the activation of caspases, which are enzymes that trigger apoptosis.
In normal cells, the regulation of c-bcl-2 protein helps to maintain a balance between cell proliferation and cell death, ensuring proper tissue homeostasis. However, when the c-bcl-2 gene is mutated or its expression is dysregulated, it can contribute to cancer development by allowing cancer cells to survive and proliferate. High levels of c-bcl-2 protein have been found in many types of cancer, including leukemia, lymphoma, and carcinomas, and are often associated with a poor prognosis.
Brain death is a legal and medical determination that an individual has died because their brain has irreversibly lost all functions necessary for life. It is characterized by the absence of brainstem reflexes, unresponsiveness to stimuli, and the inability to breathe without mechanical support. Brain death is different from a vegetative state or coma, where there may still be some brain activity.
The determination of brain death involves a series of tests and examinations to confirm the absence of brain function. These tests are typically performed by trained medical professionals and may include clinical assessments, imaging studies, and electroencephalograms (EEGs) to confirm the absence of electrical activity in the brain.
Brain death is an important concept in medicine because it allows for the organ donation process to proceed, potentially saving the lives of others. In many jurisdictions, brain death is legally equivalent to cardiopulmonary death, which means that once a person has been declared brain dead, they are considered deceased and their organs can be removed for transplantation.
Fetal death, also known as stillbirth or intrauterine fetal demise, is defined as the death of a fetus at 20 weeks of gestation or later. The criteria for defining fetal death may vary slightly by country and jurisdiction, but in general, it refers to the loss of a pregnancy after the point at which the fetus is considered viable outside the womb.
Fetal death can occur for a variety of reasons, including chromosomal abnormalities, placental problems, maternal health conditions, infections, and umbilical cord accidents. In some cases, the cause of fetal death may remain unknown.
The diagnosis of fetal death is typically made through ultrasound or other imaging tests, which can confirm the absence of a heartbeat or movement in the fetus. Once fetal death has been diagnosed, medical professionals will work with the parents to determine the best course of action for managing the pregnancy and delivering the fetus. This may involve waiting for labor to begin naturally, inducing labor, or performing a cesarean delivery.
Experiencing a fetal death can be a very difficult and emotional experience for parents, and it is important for them to receive supportive care from their healthcare providers, family members, and friends. Grief counseling and support groups may also be helpful in coping with the loss.
"Attitude to Death" is not a medical term per se, but it does refer to an individual's perspective, feelings, and beliefs about death and dying. It can encompass various aspects such as fear, acceptance, curiosity, denial, or preparation. While not a medical definition, understanding a person's attitude to death can be relevant in healthcare settings, particularly in palliative and end-of-life care, as it can influence their decisions and experiences around their own mortality.
Bcl-2 is a family of proteins that play a crucial role in regulating cell death (apoptosis), which is a normal process that eliminates damaged or unnecessary cells from the body. Specifically, Bcl-2 proteins are involved in controlling the mitochondrial pathway of apoptosis.
The bcl-2 gene provides instructions for making one member of this protein family, called B-cell lymphoma 2 protein. This protein is located primarily on the outer membrane of mitochondria and helps to prevent apoptosis by inhibiting the release of cytochrome c from the mitochondria into the cytoplasm.
In healthy cells, the balance between pro-apoptotic (promoting cell death) and anti-apoptotic (inhibiting cell death) proteins is critical for maintaining normal tissue homeostasis. However, in some cancers, including certain types of leukemia and lymphoma, the bcl-2 gene is abnormally overexpressed, leading to an excess of Bcl-2 protein that disrupts this balance and allows cancer cells to survive and proliferate.
Therefore, understanding the role of bcl-2 in apoptosis has important implications for developing new therapies for cancer and other diseases associated with abnormal cell death regulation.
Cell survival refers to the ability of a cell to continue living and functioning normally, despite being exposed to potentially harmful conditions or treatments. This can include exposure to toxins, radiation, chemotherapeutic drugs, or other stressors that can damage cells or interfere with their normal processes.
In scientific research, measures of cell survival are often used to evaluate the effectiveness of various therapies or treatments. For example, researchers may expose cells to a particular drug or treatment and then measure the percentage of cells that survive to assess its potential therapeutic value. Similarly, in toxicology studies, measures of cell survival can help to determine the safety of various chemicals or substances.
It's important to note that cell survival is not the same as cell proliferation, which refers to the ability of cells to divide and multiply. While some treatments may promote cell survival, they may also inhibit cell proliferation, making them useful for treating diseases such as cancer. Conversely, other treatments may be designed to specifically target and kill cancer cells, even if it means sacrificing some healthy cells in the process.
Proto-oncogene proteins are normal cellular proteins that play crucial roles in various cellular processes, such as signal transduction, cell cycle regulation, and apoptosis (programmed cell death). They are involved in the regulation of cell growth, differentiation, and survival under physiological conditions.
When proto-oncogene proteins undergo mutations or aberrations in their expression levels, they can transform into oncogenic forms, leading to uncontrolled cell growth and division. These altered proteins are then referred to as oncogene products or oncoproteins. Oncogenic mutations can occur due to various factors, including genetic predisposition, environmental exposures, and aging.
Examples of proto-oncogene proteins include:
1. Ras proteins: Involved in signal transduction pathways that regulate cell growth and differentiation. Activating mutations in Ras genes are found in various human cancers.
2. Myc proteins: Regulate gene expression related to cell cycle progression, apoptosis, and metabolism. Overexpression of Myc proteins is associated with several types of cancer.
3. EGFR (Epidermal Growth Factor Receptor): A transmembrane receptor tyrosine kinase that regulates cell proliferation, survival, and differentiation. Mutations or overexpression of EGFR are linked to various malignancies, such as lung cancer and glioblastoma.
4. Src family kinases: Intracellular tyrosine kinases that regulate signal transduction pathways involved in cell proliferation, survival, and migration. Dysregulation of Src family kinases is implicated in several types of cancer.
5. Abl kinases: Cytoplasmic tyrosine kinases that regulate various cellular processes, including cell growth, differentiation, and stress responses. Aberrant activation of Abl kinases, as seen in chronic myelogenous leukemia (CML), leads to uncontrolled cell proliferation.
Understanding the roles of proto-oncogene proteins and their dysregulation in cancer development is essential for developing targeted cancer therapies that aim to inhibit or modulate these aberrant signaling pathways.
Signal transduction is the process by which a cell converts an extracellular signal, such as a hormone or neurotransmitter, into an intracellular response. This involves a series of molecular events that transmit the signal from the cell surface to the interior of the cell, ultimately resulting in changes in gene expression, protein activity, or metabolism.
The process typically begins with the binding of the extracellular signal to a receptor located on the cell membrane. This binding event activates the receptor, which then triggers a cascade of intracellular signaling molecules, such as second messengers, protein kinases, and ion channels. These molecules amplify and propagate the signal, ultimately leading to the activation or inhibition of specific cellular responses.
Signal transduction pathways are highly regulated and can be modulated by various factors, including other signaling molecules, post-translational modifications, and feedback mechanisms. Dysregulation of these pathways has been implicated in a variety of diseases, including cancer, diabetes, and neurological disorders.
In the field of medicine, "time factors" refer to the duration of symptoms or time elapsed since the onset of a medical condition, which can have significant implications for diagnosis and treatment. Understanding time factors is crucial in determining the progression of a disease, evaluating the effectiveness of treatments, and making critical decisions regarding patient care.
For example, in stroke management, "time is brain," meaning that rapid intervention within a specific time frame (usually within 4.5 hours) is essential to administering tissue plasminogen activator (tPA), a clot-busting drug that can minimize brain damage and improve patient outcomes. Similarly, in trauma care, the "golden hour" concept emphasizes the importance of providing definitive care within the first 60 minutes after injury to increase survival rates and reduce morbidity.
Time factors also play a role in monitoring the progression of chronic conditions like diabetes or heart disease, where regular follow-ups and assessments help determine appropriate treatment adjustments and prevent complications. In infectious diseases, time factors are crucial for initiating antibiotic therapy and identifying potential outbreaks to control their spread.
Overall, "time factors" encompass the significance of recognizing and acting promptly in various medical scenarios to optimize patient outcomes and provide effective care.
A cell line that is derived from tumor cells and has been adapted to grow in culture. These cell lines are often used in research to study the characteristics of cancer cells, including their growth patterns, genetic changes, and responses to various treatments. They can be established from many different types of tumors, such as carcinomas, sarcomas, and leukemias. Once established, these cell lines can be grown and maintained indefinitely in the laboratory, allowing researchers to conduct experiments and studies that would not be feasible using primary tumor cells. It is important to note that tumor cell lines may not always accurately represent the behavior of the original tumor, as they can undergo genetic changes during their time in culture.
BCL-2-associated X protein, often abbreviated as BAX, is a type of protein belonging to the BCL-2 family. The BCL-2 family of proteins plays a crucial role in regulating programmed cell death, also known as apoptosis. Specifically, BAX is a pro-apoptotic protein, which means that it promotes cell death.
BAX is encoded by the BAX gene, and it functions by forming pores in the outer membrane of the mitochondria, leading to the release of cytochrome c and other pro-apoptotic factors into the cytosol. This triggers a cascade of events that ultimately leads to cell death.
Dysregulation of BAX and other BCL-2 family proteins has been implicated in various diseases, including cancer and neurodegenerative disorders. For example, reduced levels of BAX have been observed in some types of cancer, which may contribute to tumor growth and resistance to chemotherapy. On the other hand, excessive activation of BAX has been linked to neuronal death in conditions such as Alzheimer's disease and Parkinson's disease.
'Death domain receptors' (also known as 'death receptors') are a type of transmembrane receptor proteins that play a crucial role in activating programmed cell death, or apoptosis, in response to specific signals. These receptors have an intracellular domain called the 'death domain,' which can interact with other proteins to initiate the signaling cascade leading to cell death. This process is essential for maintaining tissue homeostasis and eliminating damaged, infected, or potentially cancerous cells. Examples of death domain receptors include Fas (CD95), TNFR1 (Tumor Necrosis Factor Receptor 1), and DR3 (Death Receptor 3).
CARD (caspase recruitment domain) signaling adaptor proteins are a group of intracellular signaling molecules that play a crucial role in the regulation of various cellular processes, including inflammation, immunity, and programmed cell death or apoptosis. These proteins contain a CARD domain, which is a protein-protein interaction module that enables them to bind to other CARD-containing proteins and form large signaling complexes.
CARD signaling adaptor proteins function as molecular scaffolds that help bring together various signaling components in response to different stimuli, such as pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs). By doing so, they facilitate the activation of downstream signaling cascades and the initiation of appropriate cellular responses.
Some examples of CARD signaling adaptor proteins include:
1. Myeloid differentiation factor 88 (MyD88): This protein is involved in the signaling pathways of most Toll-like receptors (TLRs) and interleukin-1 receptor (IL-1R) family members, which are critical for the detection of microbial components and the initiation of innate immune responses.
2. CARD9: This protein is involved in the signaling pathways of several C-type lectin receptors (CLRs), which recognize fungal and other pathogens, and plays a key role in antifungal immunity.
3. ASC (apoptosis-associated speck-like protein containing a CARD): This protein is involved in the formation of inflammasomes, which are large cytosolic complexes that activate caspase-1 and promote the maturation and secretion of proinflammatory cytokines.
4. RIPK2 (receptor-interacting serine/threonine-protein kinase 2): This protein is involved in the signaling pathways of NOD1 and NOD2, which are intracellular sensors of bacterial peptidoglycan, and plays a role in the regulation of inflammation and apoptosis.
Overall, CARD-containing proteins play crucial roles in various immune signaling pathways by mediating protein-protein interactions and downstream signal transduction events, ultimately leading to the activation of innate immunity and inflammatory responses.
B-cell lymphoma is a type of cancer that originates from the B-lymphocytes, which are a part of the immune system and play a crucial role in fighting infections. These cells can develop mutations in their DNA, leading to uncontrolled growth and division, resulting in the formation of a tumor.
B-cell lymphomas can be classified into two main categories: Hodgkin's lymphoma and non-Hodgkin's lymphoma. B-cell lymphomas are further divided into subtypes based on their specific characteristics, such as the appearance of the cells under a microscope, the genetic changes present in the cancer cells, and the aggressiveness of the disease.
Some common types of B-cell lymphomas include diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, and Burkitt lymphoma. Treatment options for B-cell lymphomas depend on the specific subtype, stage of the disease, and other individual factors. Treatment may include chemotherapy, radiation therapy, immunotherapy, targeted therapy, or stem cell transplantation.
Caspase-3 is a type of protease enzyme that plays a central role in the execution-phase of cell apoptosis, or programmed cell death. It's also known as CPP32 (CPP for ced-3 protease precursor) or apopain. Caspase-3 is produced as an inactive protein that is activated when cleaved by other caspases during the early stages of apoptosis. Once activated, it cleaves a variety of cellular proteins, including structural proteins, enzymes, and signal transduction proteins, leading to the characteristic morphological and biochemical changes associated with apoptotic cell death. Caspase-3 is often referred to as the "death protease" because of its crucial role in executing the cell death program.
Translocation, genetic, refers to a type of chromosomal abnormality in which a segment of a chromosome is transferred from one chromosome to another, resulting in an altered genome. This can occur between two non-homologous chromosomes (non-reciprocal translocation) or between two homologous chromosomes (reciprocal translocation). Genetic translocations can lead to various clinical consequences, depending on the genes involved and the location of the translocation. Some translocations may result in no apparent effects, while others can cause developmental abnormalities, cancer, or other genetic disorders. In some cases, translocations can also increase the risk of having offspring with genetic conditions.
Medical Definition:
"Risk factors" are any attribute, characteristic or exposure of an individual that increases the likelihood of developing a disease or injury. They can be divided into modifiable and non-modifiable risk factors. Modifiable risk factors are those that can be changed through lifestyle choices or medical treatment, while non-modifiable risk factors are inherent traits such as age, gender, or genetic predisposition. Examples of modifiable risk factors include smoking, alcohol consumption, physical inactivity, and unhealthy diet, while non-modifiable risk factors include age, sex, and family history. It is important to note that having a risk factor does not guarantee that a person will develop the disease, but rather indicates an increased susceptibility.
Human chromosome pair 14 consists of two rod-shaped structures present in the nucleus of human cells, which contain genetic material in the form of DNA and proteins. Each member of the pair contains a single very long DNA molecule that carries an identical set of genes and other genetic elements, totaling approximately 105 million base pairs. These chromosomes play a crucial role in the development, functioning, and reproduction of human beings.
Chromosome 14 is one of the autosomal chromosomes, meaning it is not involved in determining the sex of an individual. It contains around 800-1,000 genes that provide instructions for producing various proteins responsible for numerous cellular functions and processes. Some notable genes located on chromosome 14 include those associated with neurodevelopmental disorders, cancer susceptibility, and immune system regulation.
Human cells typically have 23 pairs of chromosomes, including 22 autosomal pairs (numbered 1-22) and one pair of sex chromosomes (XX for females or XY for males). Chromosome pair 14 is the eighth largest autosomal pair in terms of its total length.
It's important to note that genetic information on chromosome 14, like all human chromosomes, can vary between individuals due to genetic variations and mutations. These differences contribute to the unique characteristics and traits found among humans.
Mitochondria are specialized structures located inside cells that convert the energy from food into ATP (adenosine triphosphate), which is the primary form of energy used by cells. They are often referred to as the "powerhouses" of the cell because they generate most of the cell's supply of chemical energy. Mitochondria are also involved in various other cellular processes, such as signaling, differentiation, and apoptosis (programmed cell death).
Mitochondria have their own DNA, known as mitochondrial DNA (mtDNA), which is inherited maternally. This means that mtDNA is passed down from the mother to her offspring through the egg cells. Mitochondrial dysfunction has been linked to a variety of diseases and conditions, including neurodegenerative disorders, diabetes, and aging.
Bcl-2-associated death promoter
Bcl-2-like protein 1
Bcl-2
Bcl-2 family
Bcl-2 homologous antagonist killer
Bcl-2-interacting killer
Bcl-xL
C-Raf
Venetoclax
BNIP3
Sanford Burnham Prebys Medical Discovery Institute
MCL1
BNIP2
Phorbol-12-myristate-13-acetate-induced protein 1
Primary pigmented nodular adrenocortical disease
BCLAF1
TARBP2
Chandrima Shaha
Apoptosome
Apoptosis regulator BAX
BAG3
XIAP
BCL2L11
HRK (gene)
Ebola viral protein 24
Ferroptosis
Major facilitator superfamily
Neuroprotection
BAG1
DAD1
Bcl-2-associated death promoter - Wikipedia
Oxygen deprivation induced cell death: an update
Autophagy as a decisive process for cell death | Experimental & Molecular Medicine
Chronic Lymphocytic Leukemia | Cancer Blood & Bone Marrow
Integrating Multiple Microarray Data for Cancer Pathway Analysis Using Bootstrapping K-S Test
Glycobiology of cell death: when glycans and lectins govern cell fate | Cell Death & Differentiation
Frontiers | Cannabinoid compounds in combination with curcumin and piperine display an anti-tumorigenic effect against colon...
Figure 1 - Immune Cell Apoptosis Prevention as Potential Therapy for Severe Infections - Volume 13, Number 2-February 2007 -...
VENCLEXTA® (venetoclax) Receives FDA Full Approval for Acute Myeloid Leukemia (AML) | BioSpace
European Journal of Neuroscience
Cancer Genes | CancerQuest
Comparative Anticancer Potentials... preview & related info | Mendeley
Plus it
BioWorld Science: The Daily Drug R&D News Source
IJMS | Free Full-Text | Targeting ERK-Hippo Interplay in Cancer Therapy
Purvalanol induces endoplasmic reticulum stress-mediated apoptosis and autophagy in a time-dependent manner in HCT116 colon...
Structural perspectives on BCL-2 family of proteins<...
drop in platlets - Hepatitis C - MedHelp
Scientists Demonstrate Therapeutic Silencing of Acute Lung Injury Target
NICE approves venetoclax with obinutuzumab for patients with untreated CLL - Leukaemia Care
Clinical significance of bax/bcl-2 ratio in chronic lymphocytic leukemia | Haematologica
Cell Biology Clia | Gentaur Clia Kits | US - UK & Europe Supply
Study Shows How Eye Cells Die When Exposed To Lead | ScienceDaily
Disrupting Protein-Protein Interactions with Small Molecules | The New York Academy of Sciences
Pediatric Systemic Lupus Erythematosus: Practice Essentials, Background, Etiology
Pathology Research Laboratories | Pathology
SCOPe 2.08: Domain d6fs2b1: 6fs2 B:174-324
JCI - mTORC1 and mTORC2 selectively regulate CD8+ T cell differentiation
Plus it
Publications - Professor Michael A. ('Mike') Skinner
Kinase12
- When BAD is phosphorylated by Akt/protein kinase B (triggered by PIP3), it forms the BAD-(14-3-3) protein heterodimer. (wikipedia.org)
- Kinase proteins send signals to the cell's control center to help tumor cells grow. (cancercare.org)
- Kinase inhibitors block these proteins. (cancercare.org)
- For this purpose, WIN 55,212-2 was injected in pregnant wistar rats from gestation day 5 to 20 and a detailed analysis of the levels of the neurotrophin brain-derived neurotrophic factor (BDNF) as well as of the signaling molecules extracellular signal-regulated kinase (ERK)1/2 and alpha-calcium/calmodulin-dependent protein kinase II (alpha-CaMKII) was carried out in adult offspring. (researchgate.net)
- Extracellular signal-regulated kinase (ERK) is a part of the mitogen-activated protein kinase (MAPK) signaling pathway which allows the transduction of various cellular signals to final effectors and regulation of elementary cellular processes. (mdpi.com)
- Cyclin-dependent kinases (CDKs), are members of the serine-threonine protein kinase family and are responsible for taking control of cell cycle regulation in eukaryotic cells. (spandidos-publications.com)
- We studied measures of molecular signaling and cell death in a model of SE in mice of both sexes, including wild-type and TrkB Shc/Shc mutant mice in which a point mutation (Y515F) of TrkB prevents the binding of Shc to activated TrkB kinase. (jneurosci.org)
- Phosphorylation of residue Y515 promotes association of TrkB with the adaptor protein Shc and activation of PI3-kinase (PI3K)/Akt, MAPK signaling pathways whereas phosphorylation of residue Y816 promotes association of phospholipase Cγ1 (PLCγ1) and signaling mediated by IP3 and DAG ( Reichardt, 2006 ). (jneurosci.org)
- In addition, activation of antiapoptotic factors including phospho-Akt (protein kinase B) and Bcl-2 was detected. (cdc.gov)
- Interestingly, rbf1 -induced apoptosis leads to a debcl - and drp1 -dependent Reactive Oxygen Species production, which in turn activates the Jun Kinase pathway to trigger cell death. (sdbonline.org)
- Rhamnaceae) on cisplatin-induced damage to kidney epithelial LLC-PK1 cells via mitogen-activated protein kinase (MAPK) and apoptosis pathways. (mdpi.com)
- Its activation is tightly controlled by numerous other signaling proteins including protein kinase C (PKC), Sab/SH3BP, and caveolin-1. (medscape.com)
Anti-apoptotic proteins3
- After activation, it is able to form a heterodimer with anti-apoptotic proteins and prevent them from stopping apoptosis. (wikipedia.org)
- BCL-2 proteins are a family of pro- and anti-apoptotic proteins that regulate a critical step in the mitochondrial apoptotic pathway, the permeabilization of the mitochondrial outer membrane. (elsevierpure.com)
- It has been previously shown that rbf1 pro-apoptotic activity depends on its ability to decrease the level of anti-apoptotic proteins such as the Bcl-2 family protein Buffy. (sdbonline.org)
Inhibitors3
- Finally, the recently proposed new therapies employing bcl-2 inhibitors prompted the potential use of bax/bcl-2 ratio to identify patients putatively resistant to these molecules. (haematologica.org)
- We further demonstrated that suppression of autophagy using either pharmacological inhibitors or RNA interference of essential autophagy genes enhanced cell death induced by IM in cell lines and primary CML cells. (lu.se)
- Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. (bvsalud.org)
Mitochondrial12
- It does not contain a C-terminal transmembrane domain for outer mitochondrial membrane and nuclear envelope targeting, unlike most other members of the Bcl-2 family. (wikipedia.org)
- The anti-apoptotic Bcl-2 and Bcl-xL proteins inhibit cytochrome c release through the mitochondrial pore and also inhibit activation of the cytoplasmic caspase cascade by cytochrome c. (wikipedia.org)
- Because apoptosis and mitochondrial function play an important role in physiology and a number of diseases, intensive investigation over the past two decades has been invested to understand in detail the structure and function of the BCL-2 proteins. (elsevierpure.com)
- We will discuss the structural insights for each structural domain of BCL-2 proteins that determine their function in the cytosol and the outer mitochondrial membrane. (elsevierpure.com)
- All three triggered mitochondrial damage, caspase activation, and cell death. (medhelp.org)
- The researchers also found that an excess of an anti-death protein called Bcl-xL completely blocked the death of the eye's rod cells and maintained normal mitochondrial function in the rods throughout adulthood. (sciencedaily.com)
- BID serves as a direct molecular link between caspase 8 activation and mitochondrial death machinery. (thermofisher.com)
- This protein regulates apoptosis through controlling mitochondrial fusion and fission. (biolegend.com)
- The Drosophila retinoblastoma protein, Rbf1, induces a debcl and drp1 -dependent mitochondrial apoptosis. (sdbonline.org)
- These results provide a mechanism by which Drosophila Bcl-2 family proteins can control apoptosis and shed light on a link between Rbf1 and mitochondrial dynamics, in vivo. (sdbonline.org)
- Mitochondrial porin , also known as the voltage-dependent anion channel (VDAC), is a multi-functional channel protein that shuttles metabolites between the mitochondria and the cytosol and implicated in cellular life and death decisions. (sdbonline.org)
- The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. (bvsalud.org)
Prosurvival2
- In stark contrast, deletion of the prosurvival protein Bcl-xL resulted in megakaryocyte apoptosis and a failure of platelet shedding. (medhelp.org)
- Genetic disruption of TrkB-Shc signaling had no effect on severity of SE yet partially inhibited activation of the prosurvival adaptor protein Akt. (jneurosci.org)
Genes8
- Genes whose protein products stimulate or enhance the division and viability of cells. (cancerquest.org)
- This first category also includes genes that contribute to tumor growth by inhibiting cell death. (cancerquest.org)
- Genes whose protein products can directly or indirectly prevent cell division or lead to cell death. (cancerquest.org)
- The expression of caspase-3 and caspase-9 genes increased in HCT-116 cell lines after 48 h of treatment, suggesting cell death by the apoptotic pathways. (mendeley.com)
- mRNA levels of other genes were not affected by administration of the siRNA, including VEGF, Bcl-2, and B-actin. (genengnews.com)
- Lentivirus-mediated expression of human secreted amyloid precursor protein-alpha promotes long-term induction of neuroprotective genes and pathways in a mouse model of Alzheimer's disease. (otago.ac.nz)
- Only two Bcl-2 family genes have been found in Drosophila melanogaster including the pro-cell survival, human Bok-related orthologue, Buffy. (sdbonline.org)
- ProteÃnas de la membrana codificadas por los GENES BCL-2 y que sirven como potentes inhibidores de la muerte celular por APOPTOSIS. (bvsalud.org)
Cytochrome6
- The upstream regulators of cytochrome c release are the Bcl-2 family members. (nih.gov)
- Pro-apoptotic Bcl-2 family members such as bax or bak are clearly required to initiate cytochrome c/apaf-1/caspase-9 mediated cell death during oxygen deprivation. (nih.gov)
- Fox says Bax seems to cause channels, or pores, in the mitochondria to open up and release yet another "death factor" protein called cytochrome c. (sciencedaily.com)
- CASP8 cleaves this encoded protein, and the COOH-terminal part translocates to mitochondria where it triggers cytochrome c release. (thermofisher.com)
- Apoptotic cell death induced by metallic nickel particles in JB6 cells is through a caspase-8/AIF mediated cytochrome c-independent pathway. (cdc.gov)
- Activation of Akt and Bcl-2 may play an important role in preventing cytochrome c release from mitochondria to the cytoplasm and may also be important in the carcinogenicity of metallic nickel particles. (cdc.gov)
Lymphoma3
- Venetoclax (Venclexta) targets the B-cell lymphoma 2 (BCL-2) protein, leading to the death of CLL cells. (cancercare.org)
- 2 Bcl-2 (B-cell lymphoma-2) family of antiapoptotic (bcl-2, bcl-xl, bcl-w and mcl-1) and proapoptotic (bax, bak and bok) proteins are critical regulators of apoptosis in CLL. (haematologica.org)
- Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma. (bvsalud.org)
Antiapoptotic1
- The molecular docking studies showed favorable binding affinity against different pro- and antiapoptotic proteins by these compounds. (mendeley.com)
Autophagy11
- However, emerging evidence suggests that autophagy is a primary mechanism of cell death (autophagic cell death, ACD) and implicates ACD in several aspects of mammalian physiology, including tumor suppression and psychological disorders. (nature.com)
- Autophagy is generally considered as a cell survival/protection mechanism because it removes toxic or obsolete proteins and organelles and recycles the degradation products for use as sources for energy and metabolites in anabolic pathways 3 . (nature.com)
- Therefore, the relationship between autophagy and cell death remains unclear and warrants further study to harness autophagy for the treatment of various human diseases. (nature.com)
- Therefore, in this review, we avoid a lengthy repetition of the description of autophagy and cell death processes and focus on the death-promoting roles of autophagy and the intertwined connection between autophagy and apoptosis. (nature.com)
- We discuss here the contribution of glycan-lectin interactions to the initiation, execution and resolution of apoptosis and their emerging roles in other cell death programs including autophagy. (nature.com)
- Various physiological and pathological conditions such as glucose starvation, inhibition of protein glycosylation and oxidative stress may cause an accumulation of unfolded proteins in the endoplasmic reticulum (ER), leading to the unfolded protein response (UPR) and autophagy. (spandidos-publications.com)
- Communication between the cell survival pathway of autophagy and the cell death pathway of apoptosis is crucial for determining the best outcome for the cell, and ultimately its fate. (edu.au)
- The first is to use an in vivo approach to analyse transgenic mice in which the autophagy regulator known as Beclin has been engineered to either disrupt or enhance its regulation by key components (i.e. proteins) of the apoptosis pathways. (edu.au)
- The second approach is to use either the new gene editing CRISPR/Cas9 technology or mass spectrometric/proteomics approaches (or both) to undertake screens to identify factors that can inhibit the cell death that occurs as a consequence of disarming the autophagy pathway through deletion of Beclin. (edu.au)
- Furthermore, As increased the levels of apoptosis and autophagy proteins in cortex, while Mel (20 mg/kg) decreased apoptosis and autophagy. (bvsalud.org)
- IM-induced autophagy did not involve c-Abl or Bcl-2 activity but was associated with ER stress and was suppressed by depletion of intracellular Ca2+, suggesting it is mechanistically. (lu.se)
Phosphorylation2
- Phosphorylation of Bcl-2 has been shown to enhance activity to allow response to extracellular growth-factor-mediated signals. (biolegend.com)
- Furthermore, in influenza A virus-infected cells, TG6-44 treatment led to suppression of virus-induced cell death as evidenced by decreased caspase-3 activation, decreased proportion of Annexin V+PI+ cells, and increased Bcl-2 phosphorylation. (cdc.gov)
Venetoclax2
- Venetoclax is an oral BCL-2 inhibitor. (leukaemiacare.org.uk)
- Venetoclax inhibits and blocks this activity of the BCL-2 protein, causing cell death of CLL cells. (leukaemiacare.org.uk)
Survival16
- Understanding the function of lectin-glycan recognition systems in cell death will facilitate the implementation of novel therapeutic strategies aimed at controlling unbalanced cell proliferation and survival in several pathologic conditions. (nature.com)
- However, the precise role of lcn2 in the cell survival and death has yet to be determined. (jneurosci.org)
- In multivariate analysis of progression-free survival and overall survival, bax/bcl-2 was an independent prognostic factor ( P =0.0002 and P =0.002). (haematologica.org)
- 3 In particular, bcl-2 has emerged as the most important protein in predicting survival in CLL between 11 proteins that are implicated in the control of apoptosis, proliferation and differentiation. (haematologica.org)
- The BCL-2 protein prevents programmed cell death and thereby supports the survival of leukaemia cells. (leukaemiacare.org.uk)
- Taken all together this demonstrates a role for Buffy, a Bcl-2 pro-cell survival gene, in neuroprotection. (sdbonline.org)
- Our aim is to develop new reagents, including drugs that could target and inhibit the actions of the key pro-survival protein proteins that keep cancers alive. (edu.au)
- There is some evidence that Bcl-2 pro-survival proteins (which normally keep cells alive by inhibiting the cell death program of apoptosis) are expressed at unusually high levels in melanoma compared to normal melanocytes. (edu.au)
- Our hypothesis is that Bcl-2 pro-survival proteins provide a survival advantage for melanomas and might contribute to resistance to standard chemotherapeutic drugs. (edu.au)
- Our research aims to identify the key Bcl-2 pro-survival proteins that are responsible for melanoma survival. (edu.au)
- The second aim is to determine whether resistance to current melanoma treatment arises due to elevated levels of Bcl-2 pro-survival proteins, and whether treatment with Bcl-2-targeting molecules will resensitise tumours to standard drugs, informing potential drug treatment combinations. (edu.au)
- Cells possess distinct pathways that promote their survival or death. (edu.au)
- Results from this work will significantly advance our understanding of how the interplay between cell death and cell survival is regulated, which is still poorly understood despite its considerable biological importance. (edu.au)
- Our laboratory uses biochemical, genetic, and cell biology approaches to investigate the molecular mechanisms of cell death and survival in cancer cells. (unmc.edu)
- We aim to understand how these proteins function as major regulators of cell death and survival, and hope to contribute to the design of more powerful and selective cancer therapeutic drugs. (unmc.edu)
- Elimination of BCR/ABL-dependent intracellular signals triggers apoptosis, but it is unclear whether this activates additional cell survival and/or death pathways. (lu.se)
Molecules2
- Two decades later, pioneering studies suggested that lectin-like molecules constitutively expressed on the surface of macrophages can selectively recognize changes on glycans decorating the surface of apoptotic thymocytes, 4 , 5 although these studies likewise did not provide substantial insight into the mechanisms by which lectin-glycan interactions regulate cell death. (nature.com)
- Moreover, the recently proposed anti-bcl-2 molecules, such as ABT-199, have emphasized the potential role of of bcl-2 family proteins in the context of target therapies. (haematologica.org)
Mitochondria2
- But when a cell is damaged, the mitochondria become the "central executioners," releasing proteins sequestered within them that are death signals for the cell. (sciencedaily.com)
- A higher level of calcium within the mitochondria sensitizes the mitochondria to interact with a "death factor" protein produced by the cell called Bax. (sciencedaily.com)
Therapies1
- Cross-talk of the MAPK signaling pathway with other proteins and signaling pathways have a crucial impact on clinical outcomes of targeted therapies and plays important role during development of drug resistance in cancers. (mdpi.com)
Family17
- The BCL2 associated agonist of cell death (BAD) protein is a pro-apoptotic member of the Bcl-2 gene family which is involved in initiating apoptosis. (wikipedia.org)
- BAD is a member of the BH3-only family, a subfamily of the Bcl-2 family. (wikipedia.org)
- Here we review what is currently known oxygen deprivation induced cell death and speculate about initiating mechanisms resulting in the activation of pro-apoptotic Bcl-2 family members. (nih.gov)
- Structural biology investigations of BCL-2 proteins have provided tremendous insights into our understanding of their structure-function relationships and models have been proposed to explain how the BCL-2 family members form a network of interactions to control apoptosis signaling. (elsevierpure.com)
- Furthermore, we will discuss the structural details of the interactions between BCL-2 family members and the various structural paradigms that ultimately regulate the activation of apoptosis. (elsevierpure.com)
- Gavathiotis, E 2014, Structural perspectives on BCL-2 family of proteins . (elsevierpure.com)
- In chronic lymphocytic leukemia the balance between the pro-apoptotic and anti-apoptotic members of the bcl-2 family is involved in the pathogenesis, chemorefractoriness and clinical outcome. (haematologica.org)
- We use a multidisciplinary approach to study select pro-apoptotic BCL-2 family proteins. (yale.edu)
- Bid is a member of the BCL-2 family of cell death regulators. (thermofisher.com)
- BID is also a pro-apoptotic member of the Bcl 2 family. (thermofisher.com)
- It forms homodimers or heterodimers with other Bcl-2 family members. (biolegend.com)
- Using a computer modeling approach that they developed, MIT biologists identified three different proteins that can bind selectively to each of three similar targets, all members of the Bcl-2 family of proteins. (mit.edu)
- In a paper appearing in the Proceedings of the National Academy of Sciences the week of Oct. 15, Keating and her colleagues used this approach to generate several peptides that can target different members of a protein family called Bcl-2, which help to drive cancer growth. (mit.edu)
- To create this model, the researchers first chose about 10,000 peptides, each 23 amino acids in length and helical in structure, and tested their binding to three different members of the Bcl-2 family. (mit.edu)
- Buffy often acts opposite to Debcl , the other Drosophila Bcl-2-family protein. (sdbonline.org)
- The Bcl-2 family proteins, which are classified into BH3-only, effectors Bax/Bak, and anti-apoptotic Bcl-2 proteins, are of particular interest to us. (unmc.edu)
- Lead-induced apoptosis in PC 12 cells: involvement of p53, Bcl-2 family and caspase-3. (who.int)
Overexpression1
- Chromosome 18q21.3 translocation and overexpression of Bcl-2 is frequently observed in follicular lymphomas and some diffuse large B-cell lymphomas. (biolegend.com)
Amino acids1
- In addition to its role in glucose metabolism, this pathway also regulates the redirection of free amino acids to protein synthesis via the mTOR-signaling pathway. (hindawi.com)
Proapoptotic2
- Western-blot analysis showed an activation of proapoptotic factors including Fas (CD95), Fas-associated protein with death domain (FADD), caspase-8, death receptor 3 (DR3) and BID in apoptotic cells induced by metallic nickel particles. (cdc.gov)
- The present findings suggest that local IFN production may interact with a genetic factor ( PTPN2 ) to induce aberrant proapoptotic activity of the BH3-only protein Bim, resulting in increased β-cell apoptosis via JNK activation and the intrinsic apoptotic pathway. (diabetesjournals.org)
Caspase2
- Communication between the pathways exists through cleavage of Bcl-2 interacting domain (Bid) by active caspase-8 to form truncated Bid (tBid). (cdc.gov)
- The docking scores were minimum as compared to the caspase-9, caspase-3, Bcl-xl, and JAK2. (mendeley.com)
Immunotherapy1
- This aim will also explore whether immunotherapy approaches could benefit from Bcl-2 targeting. (edu.au)
Signals2
- Glycans, either alone or complexed with glycan-binding proteins, can deliver intracellular signals or control extracellular processes that promote initiation, execution and resolution of cell death programs. (nature.com)
- Endogenous lectins and glycans are critical signals in the resolution of cell death. (nature.com)
Inhibitor1
- BCL-2 inhibitor. (cancercare.org)
Glial fibrill3
- LCN2 protein induced upregulation of glial fibrillary acidic protein (GFAP), cell migration, and morphological changes similar to characteristic phenotypic changes termed reactive astrocytosis. (jneurosci.org)
- In this process, astrocytes proliferate to fill gaps and undergo a typical morphological change: a large cytoplasmic mass, long and branched processes, and increased expression of intermediate filaments such as glial fibrillary acidic protein (GFAP). (jneurosci.org)
- It also downregulated the expression of glial fibrillary acidic protein and reduced retinal reactive gliosis. (molvis.org)
Apoptotic cell3
- Moreover, we determined that during purvalanol-mediated ER stress, autophagic machinery was also activated prior to apoptotic cell death finalization. (spandidos-publications.com)
- Τheir impact on the apoptotic cell death mechanism requires further elucidation. (spandidos-publications.com)
- Although purvalanol-induced cell cycle arrest and apoptotic cell death were demonstrated in prostate ( 5 ), breast ( 6 ) and colon cancer cells ( 7 ), the exact molecular mechanism of purvanol-induced apoptosis has not been elucidated yet. (spandidos-publications.com)
Pathway2
- The extrinsic pathway is mediated by a variety of death receptor ligands, including tumor necrosis factor (TNF) and Fas ligand (FaSL), that trigger apoptosis by binding to cell surface receptors. (cdc.gov)
- They also examine the involvement of cell death programs in various pathologies and the therapeutic potential of inhibiting key pathway components. (cshlpress.com)
Gene4
- Note that by convention gene names are italicized and the proteins they make are not. (cancerquest.org)
- As an example TP 53 refers to the gene and p53 refers to the protein. (cancerquest.org)
- Activated and released IRE1α acts as an RNase to initiate transcription of XBP1 mRNA and it becomes a transcriptional activator for unfolded protein response (UPR) gene targets, such as BiP and calreticulin ( 10 ). (spandidos-publications.com)
- Res effectively suppress the cardiomyocytes hypertrophy and apoptosis induced by ISO, characterized by the reduction of the myocardial cell surface area, the ANP gene expression, the LDH and MDA leakage amount and the rate of cell apoptosis, while decrease of the protein expression of GRP78, GRP94 and CHOP, and reverse the expression of Bcl-2 and Bax. (karger.com)
Target protein2
- The antigen corresponds to amino acid range 1-195 of the target protein. (thermofisher.com)
- The new strategy involves first creating a computer model that can relate peptide sequences to their binding affinity for the target protein. (mit.edu)
Genetic1
- Importantly, genetic disruption of TrkB-Shc signaling exacerbated hippocampal neuronal death induced by SE. (jneurosci.org)
Antibody1
- Obinutuzumab is a monoclonal antibody that targets the CD20 protein on the surface of leukaemia cells. (leukaemiacare.org.uk)
Inhibit1
- This leaves Bcl-2 free to inhibit Bax-triggered apoptosis. (wikipedia.org)
Antagonist1
- BID is a death agonist that heterodimerizes with either agonist BAX or antagonist BCL2. (thermofisher.com)
Activation2
- Although activation of TrkB signaling promotes development of epilepsy in this context, it also reduces SE-induced neuronal death. (jneurosci.org)
- Here we reveal that TrkB-mediated activation of Akt protects against hippocampal neuronal death in vivo following status epilepticus. (jneurosci.org)
Assay2
- Development of a high-throughput fluorescence polarization assay for Bcl-x(L)". Anal. (wikipedia.org)
- Rarely, patients have no M-protein in blood and urine, although the currently used serum free light chain assay now demonstrates monoclonal light chains in many of these formerly so-called nonsecretory patients. (msdmanuals.com)
Mediator2
- We propose that lcn2 is an autocrine mediator of reactive astrocytosis based on the multiple roles of lcn2 in the regulation of cell death, morphology, and migration of astrocytes. (jneurosci.org)
- Iron and BIM (Bcl-2-interacting mediator of cell death) proteins were involved in the cytotoxic sensitization process. (jneurosci.org)
Targets2
- New approach generates a wider variety of protein sequences optimized to bind to drug targets. (mit.edu)
- Another desirable feature is the ability to identify proteins that bind tightly to their target but not to similar targets, which helps to ensure that drugs do not have unintended side effects. (mit.edu)
Mechanism3
- ER alerts a self-protective mechanism that is called ER stress during nutrient deprivation, pathogen infection, alterations in redox status, intraluminal Ca 2+ levels and folding defective protein conditions ( 9 ). (spandidos-publications.com)
- In Cell Death: Mechanism and Disease (Vol. 9781461493020, pp. 229-251). (elsevierpure.com)
- Cell Death: Mechanism and Disease. (elsevierpure.com)
Structural3
- At that time, glycobiology, which is the study of carbohydrates and their recognition by motif-specific carbohydrate-binding proteins or lectins, lagged far behind the studies that defined the structural and cellular biology of cell death. (nature.com)
- RNA viruses may escape acquired humoral and cellular immune responses by mutations in protective antigenic epitopes (e.g., avian influenza viruses), while accessory nonstructural proteins or multifunctional structural proteins interfere with the interferon system (e.g. (imperial.ac.uk)
- SCOPe: Structural Classification of Proteins - extended. (berkeley.edu)
Members1
- That is the standard approach: Either completely randomly, or with some prior knowledge, design a library of proteins, and then go fishing in the library to pull out the most promising members," Keating says. (mit.edu)
Synthesis3
- Endoplasmic reticulum (ER) is an essential organelle responsible for protein synthesis, folding, post-translational modification of proteins and protein trafficking in eukaryotes ( 8 ). (spandidos-publications.com)
- I have a lot of experience in the following methodologies: protein isolation, protein synthesis assays, Western blotting, genotyping, RNA isolation and qPCR miRNA/mRNA arrays, bioinformatics and statistical analyses. (otago.ac.nz)
- Glutamate receptor trafficking and protein synthesis mediate the facilitation of LTP by secreted amyloid precursor protein-alpha. (otago.ac.nz)
Transcription1
- The Nobel Prize-winning modification that prevents the innate immune system from recognizing injected mRNA as foreign and blocking transcription of the protein it encodes has been found on some occasions to cause ribosomal frameshifting. (bioworld.com)
Extracellular1
- What is the precise role of intracellular and extracellular galectins in the control of cell death programs? (nature.com)
Sequences2
- MIT biologists have now come up with a more refined approach in which they use computer modeling to predict how different protein sequences will interact with the target. (mit.edu)
- The usual method for identifying such drugs is to screen millions of proteins, either randomly chosen or selected by creating variants of protein sequences already shown to be promising candidates. (mit.edu)
Cells6
- In the complete absence of oxygen, cells undergo cell death through apoptosis, and not necrosis. (nih.gov)
- In multicellular organisms, cell death is required for normal development, homeostasis, and the elimination of infected or injured cells. (cshlpress.com)
- The best studied is apoptosis, a form of programmed cell death used by all multicellular organisms to eliminate cells that are damaged, no longer needed or which might become a threat to the organism. (edu.au)
- Infants suffering of cell death occurring as a series of changes from chronic illnesses, chromosomal abnor- in dying cells under several physiological malities and those on medication prior to conditions [ 6,7 ] and has been implicated enrolment were excluded from the study. (who.int)
- Diagnosis typically requires demonstration of M-protein (sometimes present in urine and not serum but rarely absent entirely) and/or light-chain proteinuria, and excessive plasma cells in the bone marrow. (msdmanuals.com)
- In 15 to 20% of patients, plasma cells secrete only Bence Jones protein. (msdmanuals.com)
Mechanisms3
- Fox's latest animal study in PNAS sheds some light on the mechanisms responsible for lead-mediated cell death, or apoptosis, in the eye, and may suggest possible treatment options for patients suffering from various forms of retinal degeneration. (sciencedaily.com)
- The mechanisms by which cell death occurs are genetically encoded and carefully controlled. (cshlpress.com)
- Chapters are additionally devoted to cell death signaling mechanisms in plants and lower organisms, as well as the evolution of those mechanisms and the influence of pathogens that seek to evade them. (cshlpress.com)
Tumor1
- In accordance with its tumor suppressor role, the Retinoblastoma protein pRb can ensure pro-apoptotic functions. (sdbonline.org)
Regulate2
- Some proto-oncogenes work to regulate cell death. (cancerquest.org)
- The mutant proteins often retain some of their capabilities but are no longer sensitive to the controls that regulate the normal form of the protein. (cancerquest.org)
Induce cell death1
- Our results suggest that lcn2 acts in an autocrine manner to induce cell death sensitization and morphological changes in astrocytes under inflammatory conditions and that these phenotypic changes may be the basis of reactive astrocytosis in vivo . (jneurosci.org)
Clinical1
- We investigated bax/bcl-2 ratio by flow cytometry in 502 patients and identified a cut off of 1.50 to correlate bax/bcl-2 ratio with well-established clinical and biological prognosticators. (haematologica.org)
Inhibition1
- They demonstrated inhibition of acute lung injury and cell death in animals with administration of siRNAs targeting Ang2 . (genengnews.com)
Leukemia2
- Bax/bcl-2 was 1.50 or over in 263 patients (52%) with chronic lymphocytic leukemia. (haematologica.org)
- In conclusion, we defined the prognostic power of bax/bcl-2 ratio, as determined by a flow cytometric approach, and highlighted a correlation with chemoresistance and outcome in chronic lymphocytic leukemia. (haematologica.org)
Receptors1
- Glycosylation of classical death receptors fine-tunes cell death programs. (nature.com)
Mitochondrion2
- The key to most cell death is a structure within each cell called the mitochondrion, which is known primarily as the central component responsible for generating energy for the cell. (sciencedaily.com)
- Both proteins can localize at the mitochondrion , but the way they control apoptosis still remains unclear. (sdbonline.org)
Molecular1
- In addition, cell death subroutines have been recently classified on the basis of mechanical and molecular aspects of cell death processes 5 . (nature.com)