Cyclin-Dependent Kinase 2
Cyclin-Dependent Kinase 4
Cyclin-Dependent Kinase Inhibitor p27
Cyclin-Dependent Kinase Inhibitor p21
Cyclin-Dependent Kinase 5
Cell Cycle Proteins
CDC2 Protein Kinase
Cyclin-Dependent Kinase Inhibitor p16
Cyclin-Dependent Kinase Inhibitor Proteins
Cyclin-Dependent Kinase 6
Cyclin-Dependent Kinase Inhibitor p57
Tumor Suppressor Proteins
E2F1 Transcription Factor
Tumor Cells, Cultured
Tumor Suppressor Protein p53
MAP Kinase Signaling System
Transcription Factor DP1
E2F Transcription Factors
Calcium-Calmodulin-Dependent Protein Kinases
Proliferating Cell Nuclear Antigen
Molecular Sequence Data
Protein Kinase C
Reverse Transcriptase Polymerase Chain Reaction
Amino Acid Sequence
p38 Mitogen-Activated Protein Kinases
Cyclic AMP-Dependent Protein Kinases
Mitogen-Activated Protein Kinase 1
Gene Expression Regulation
Mitogen-Activated Protein Kinase Kinases
Mitogen-Activated Protein Kinase 3
JNK Mitogen-Activated Protein Kinases
Calcium-Calmodulin-Dependent Protein Kinase Type 2
MAP Kinase Kinase Kinases
Recombinant Fusion Proteins
Casein Kinase II
Intracellular Signaling Peptides and Proteins
Ribosomal Protein S6 Kinases
Mitogen-Activated Protein Kinases
MAP Kinase Kinase 1
Extracellular Signal-Regulated MAP Kinases
Glycogen Synthase Kinase 3
RNA, Small Interfering
Promoter Regions, Genetic
Receptor Protein-Tyrosine Kinases
MAP Kinase Kinase 4
Saccharomyces cerevisiae Proteins
Phosphotransferases (Alcohol Group Acceptor)
I-kappa B Kinase
Proto-Oncogene Proteins c-akt
E2F4 Transcription Factor
Protein Structure, Tertiary
Protein Kinase C-alpha
S Phase Cell Cycle Checkpoints
Protein Kinase C-delta
Gene Expression Regulation, Neoplastic
AMP-Activated Protein Kinases
Dose-Response Relationship, Drug
Sequence Homology, Amino Acid
Retinoblastoma-Binding Protein 1
Focal Adhesion Kinase 1
Janus Kinase 2
Focal Adhesion Protein-Tyrosine Kinases
Ribosomal Protein S6 Kinases, 90-kDa
TOR Serine-Threonine Kinases
Protein Kinase C-epsilon
MAP Kinase Kinase 2
MAP Kinase Kinase Kinase 1
Protein Kinase C beta
Gene Expression Regulation, Enzymologic
Cyclic GMP-Dependent Protein Kinases
Adaptor Proteins, Signal Transducing
Mitogen-Activated Protein Kinase 8
Casein Kinase I
MAP Kinase Kinase 6
Tat activates human immunodeficiency virus type 1 transcriptional elongation independent of TFIIH kinase. (1/252)Tat stimulates human immunodeficiency virus type 1 (HIV-1) transcriptional elongation by recruitment of the human transcription elongation factor P-TEFb, consisting of Cdk9 and cyclin T1, to the HIV-1 promoter via cooperative binding to the nascent HIV-1 transactivation response RNA element. The Cdk9 kinase activity has been shown to be essential for P-TEFb to hyperphosphorylate the carboxy-terminal domain (CTD) of RNA polymerase II and mediate Tat transactivation. Recent reports have shown that Tat can also interact with the multisubunit transcription factor TFIIH complex and increase the phosphorylation of CTD by the Cdk-activating kinase (CAK) complex associated with the core TFIIH. These observations have led to the proposal that TFIIH and P-TEFb may act sequentially and in a concerted manner to promote phosphorylation of CTD and increase polymerase processivity. Here, we show that under conditions in which a specific and efficient interaction between Tat and P-TEFb is observed, only a weak interaction between Tat and TFIIH that is independent of critical amino acid residues in the Tat transactivation domain can be detected. Furthermore, immunodepletion of CAK under high-salt conditions, which allow CAK to be dissociated from core-TFIIH, has no effect on either basal HIV-1 transcription or Tat activation of polymerase elongation in vitro. Therefore, unlike the P-TEFb kinase activity that is essential for Tat activation of HIV-1 transcriptional elongation, the CAK kinase associated with TFIIH appears to be dispensable for Tat function. (+info)
The transcriptional inhibitors, actinomycin D and alpha-amanitin, activate the HIV-1 promoter and favor phosphorylation of the RNA polymerase II C-terminal domain. (2/252)Actinomycin D and alpha-amanitin are commonly used to inhibit transcription. Unexpectedly, however, the transcription of the human immunodeficiency virus (HIV-1) long terminal repeats (LTR) is shown to be activated at the level of elongation, in human and murine cells exposed to these drugs, whereas the Rous sarcoma virus LTR, the human cytomegalovirus immediate early gene (CMV), and the HSP70 promoters are repressed. Activation of the HIV LTR is independent of the NFkappaB and TAR sequences and coincides with an enhanced average phosphorylation of the C-terminal domain (CTD) from the largest subunit of RNA polymerase II. Both the HIV-1 LTR activation and the bulk CTD phosphorylation enhancement are prevented by several CTD kinase inhibitors, including 5, 6-dichloro-1-beta-D-ribofuranosylbenzimidazole. The efficacies of the various compounds to block CTD phosphorylation and transcription in vivo correlate with their capacities to inhibit the CDK9/PITALRE kinase in vitro. Hence, the positive transcription elongation factor, P-TEFb, is likely to contribute to the average CTD phosphorylation in vivo and to the activation of the HIV-1 LTR induced by actinomycin D. (+info)
Human and rodent transcription elongation factor P-TEFb: interactions with human immunodeficiency virus type 1 tat and carboxy-terminal domain substrate. (3/252)The human immunodeficiency virus type 1 transcriptional regulator Tat increases the efficiency of elongation, and complexes containing the cellular kinase CDK9 have been implicated in this process. CDK9 is part of the Tat-associated kinase TAK and of the elongation factor P-TEFb (positive transcription elongation factor-b), which consists minimally of CDK9 and cyclin T. TAK and P-TEFb are both able to phosphorylate the carboxy-terminal domain (CTD) of RNA polymerase II, but their relationships to one another and to the stimulation of elongation by Tat are not well characterized. Here we demonstrate that human cyclin T1 (but not cyclin T2) interacts with the activation domain of Tat and is a component of TAK as well as of P-TEFb. Rodent (mouse and Chinese hamster) cyclin T1 is defective in Tat binding and transactivation, but hamster CDK9 interacts with human cyclin T1 to give active TAK in hybrid cells containing human chromosome 12. Although TAK is phosphorylated on both serine and threonine residues, it specifically phosphorylates serine 5 in the CTD heptamer. TAK is found in the nuclear and cytoplasmic fractions of human cells as a large complex (approximately 950 kDa). Magnesium or zinc ions are required for the association of Tat with the kinase. We suggest a model in which Tat first interacts with P-TEFb to form the TAK complex that engages with TAR RNA and the elongating transcription complex, resulting in hyperphosphorylation of the CTD on serine 5 residues. (+info)
Transcriptional regulation by targeted recruitment of cyclin-dependent CDK9 kinase in vivo. (4/252)The CDK9 kinase in association with Cyclin T is a component of the transcription positive-acting complex pTEFb which facilitates the transition from abortive to productive transcription elongation by phosphorylating the carboxyl-terminal domain of RNA polymerase II. The Cyclin T1/CDK9 complex is implicated in Tat transactivation, and it has been suggested that Tat functions by recruiting this complex to RNAPII through cooperative binding to RNA. Here, we demonstrate that targeted recruitment of Cyclin T1/CDK9 kinase complex to specific promoters, through fusion to a DNA-binding domain of either Cyclin T1 or CDK9 kinase, stimulates transcription in vivo. Transcriptional enhancement was dependent on active CDK9, as a catalytically inactive form had no transcriptional effect. We determined that, unlike conventional activators, DNA-bound CDK9 does not activate enhancerless TATA-promoters unless TBP is overexpressed, suggesting that CDK9 acts in vivo at a step subsequent to TFIID recruitment DNA-bound. Finally, we determined that CDK9-mediated transcriptional activation is mediated by preferentially stimulating productive transcription elongation. (+info)
B cell antigen receptor-mediated activation of cyclin-dependent retinoblastoma protein kinases and inhibition by co-cross-linking with Fc gamma receptors. (5/252)Cross-linking the B cell Ag receptor (BCR) to surface Fc receptors for IgG (Fc gamma R) inhibits G1-to-S progression; the mechanism by which this occurs is not completely known. We investigated the regulation of three key cell cycle regulatory components by BCR-Fc gamma R co-cross-linking: G1-cyclins, cyclin-dependent kinases (Cdks), and the retinoblastoma gene product (Rb). Rb functions to suppress G1-to-S progression in mammalian cells. Rb undergoes cell-cycle-dependent phosphorylation, leading to its inactivation and thereby promoting S phase entry. We demonstrate in this paper for the first time that BCR-induced Rb phosphorylation is abrogated by co-cross-linking with Fc gamma R. The activation of Cdk4/6- and Cdk2-dependent Rb protein kinases is concomitantly blocked. Fc gamma R-mediated inhibition of Cdk2 activity results in part from an apparent failure to express Cdk2 protein. By contrast, inhibition of Cdk4/6 activities is not due to suppression of Cdk4/6 or cyclins D2/D3 expression or inhibition of Cdk-activating kinase activity. Cdk4- and Cdk6-immune complexes recovered from B cells following BCR-Fc gamma R co-cross-linking are devoid of coprecipitated D-type cyclins, indicating that inhibition of their Rb protein kinase activities is due in part to the absence of bound D-type cyclin. Thus, BCR-derived activation signals that up-regulate D-type cyclin and Cdk4/6 protein expression remain intact; however, Fc gamma R-mediated signals block cyclin D-Cdk4/6 assembly or stabilization. These results suggest that assembly or stabilization of D-type cyclin holoenzyme complexes 1) is an important step in the activation of Cdk4/6 by BCR signals, and 2) suffice in providing a mechanism to account for inhibition of BCR-stimulated Rb protein phosphorylation by Fc gamma R. (+info)
Cyclin K functions as a CDK9 regulatory subunit and participates in RNA polymerase II transcription. (6/252)Important progress in the understanding of elongation control by RNA polymerase II (RNAPII) has come from the recent identification of the positive transcription elongation factor b (P-TEFb) and the demonstration that this factor is a protein kinase that phosphorylates the carboxyl-terminal domain (CTD) of the RNAPII largest subunit. The P-TEFb complex isolated from mammalian cells contains a catalytic subunit (CDK9), a cyclin subunit (cyclin T1 or cyclin T2), and additional, yet unidentified, polypeptides of unknown function. To identify additional factors involved in P-TEFb function we performed a yeast two-hybrid screen using CDK9 as bait and found that cyclin K interacts with CDK9 in vivo. Biochemical analyses indicate that cyclin K functions as a regulatory subunit of CDK9. The CDK9-cyclin K complex phosphorylated the CTD of RNAPII and functionally substituted for P-TEFb comprised of CDK9 and cyclin T in in vitro transcription reactions. (+info)
Requirement for a kinase-specific chaperone pathway in the production of a Cdk9/cyclin T1 heterodimer responsible for P-TEFb-mediated tat stimulation of HIV-1 transcription. (7/252)Tat activation of HIV-1 transcription is mediated by human transcription elongation factor P-TEFb, which interacts with Tat and phosphorylates the C-terminal domain of RNA polymerase II. The catalytic subunit of the P-TEFb complex, Cdk9, has been shown to interact with cyclin T and several other proteins of unknown identity. Consequently, the exact subunit composition of active P-TEFb has not been determined. Here we report the affinity purification and identification of the Cdk9-associated proteins. In addition to forming a heterodimer with cyclin T1, Cdk9 interacted with the molecular chaperone Hsp70 or a kinase-specific chaperone complex, Hsp90/Cdc37, to form two separate chaperone-Cdk9 complexes. Although the Cdk9/cyclin T1 dimer was exceptionally stable and produced slowly in the cell, free and unprotected Cdk9 appeared to be degraded rapidly. Several lines of evidence indicate the heterodimer of Cdk9/cyclin T1 to be the mature, active form of P-TEFb responsible for phosphorylation of the C-terminal domain of RNA polymerase II interaction with the Tat activation domain, and mediation of Tat activation of HIV-1 transcription. Pharmacological inactivation of Hsp90/Cdc37 function by geldanamycin revealed an essential role for the chaperone-Cdk9 complexes in generation of Cdk9/cyclin T1. Our data suggest a previously unrecognized chaperone-dependent pathway involving the sequential actions of Hsp70 and Hsp90/Cdc37 in the stabilization/folding of Cdk9 as well as the assembly of an active Cdk9/cyclin T1 complex responsible for P-TEFb-mediated Tat transactivation. (+info)
Physical interaction between CDK9 and B-Myb results in suppression of B-Myb gene autoregulation. (8/252)B-Myb is a transcription factor belonging to the myb family, whose activity has been associated with augmented DNA synthesis and cell cycle progression. We showed recently that B-Myb autoregulates its own expression through promoter transactivation. We report in this study that CDK9, the cyclin T associated kinase, which phosphorylates and activates RNA-Polymerase II, suppresses B-Myb autoregulation through direct interaction with the carboxyl-terminus of the B-Myb protein. Down-regulation of the transactivating ability of B-Myb is independent of the kinase activity of CDK9, because a kinase deficient mutant (dn-CDK9) also represses B-myb gene autoregulation. Overexpression of CDK9 did not result in suppression of p53-dependent transactivation or inhibition of the basal activity of the promoters tested so far, demonstrating that CDK9 is a B-Myb-specific repressor. Rather, transfection of the dominant negative dn-CDK9 construct inhibited the basal activity of the reporter genes, confirming an essential role for CDK9 in gene transcription. In addition, Cyclin T1 restores B-Myb transactivating activity when co-transfected along with CDK9, suggesting that the down-regulatory effect observed on B-Myb is specifically due to CDK9 alone. Thus, our data suggest that CDK9 is involved in the negative regulation of activated transcription mediated by certain transcription factors, such as B-Myb. This may indicate the existence of a feedback loop, mediated by the different activities of CDK9, which links basal with activated transcription. (+info)
There are different types of Breast Neoplasms such as:
1. Fibroadenomas: These are benign tumors that are made up of glandular and fibrous tissues. They are usually small and round, with a smooth surface, and can be moved easily under the skin.
2. Cysts: These are fluid-filled sacs that can develop in both breast tissue and milk ducts. They are usually benign and can disappear on their own or be drained surgically.
3. Ductal Carcinoma In Situ (DCIS): This is a precancerous condition where abnormal cells grow inside the milk ducts. If left untreated, it can progress to invasive breast cancer.
4. Invasive Ductal Carcinoma (IDC): This is the most common type of breast cancer and starts in the milk ducts but grows out of them and invades surrounding tissue.
5. Invasive Lobular Carcinoma (ILC): It originates in the milk-producing glands (lobules) and grows out of them, invading nearby tissue.
Breast Neoplasms can cause various symptoms such as a lump or thickening in the breast or underarm area, skin changes like redness or dimpling, change in size or shape of one or both breasts, discharge from the nipple, and changes in the texture or color of the skin.
Treatment options for Breast Neoplasms may include surgery such as lumpectomy, mastectomy, or breast-conserving surgery, radiation therapy which uses high-energy beams to kill cancer cells, chemotherapy using drugs to kill cancer cells, targeted therapy which uses drugs or other substances to identify and attack cancer cells while minimizing harm to normal cells, hormone therapy, immunotherapy, and clinical trials.
It is important to note that not all Breast Neoplasms are cancerous; some are benign (non-cancerous) tumors that do not spread or grow.
Explanation: Neoplastic cell transformation is a complex process that involves multiple steps and can occur as a result of genetic mutations, environmental factors, or a combination of both. The process typically begins with a series of subtle changes in the DNA of individual cells, which can lead to the loss of normal cellular functions and the acquisition of abnormal growth and reproduction patterns.
Over time, these transformed cells can accumulate further mutations that allow them to survive and proliferate despite adverse conditions. As the transformed cells continue to divide and grow, they can eventually form a tumor, which is a mass of abnormal cells that can invade and damage surrounding tissues.
In some cases, cancer cells can also break away from the primary tumor and travel through the bloodstream or lymphatic system to other parts of the body, where they can establish new tumors. This process, known as metastasis, is a major cause of death in many types of cancer.
It's worth noting that not all transformed cells will become cancerous. Some forms of cellular transformation, such as those that occur during embryonic development or tissue regeneration, are normal and necessary for the proper functioning of the body. However, when these transformations occur in adult tissues, they can be a sign of cancer.
See also: Cancer, Tumor
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1) They share similarities with humans: Many animal species share similar biological and physiological characteristics with humans, making them useful for studying human diseases. For example, mice and rats are often used to study diseases such as diabetes, heart disease, and cancer because they have similar metabolic and cardiovascular systems to humans.
2) They can be genetically manipulated: Animal disease models can be genetically engineered to develop specific diseases or to model human genetic disorders. This allows researchers to study the progression of the disease and test potential treatments in a controlled environment.
3) They can be used to test drugs and therapies: Before new drugs or therapies are tested in humans, they are often first tested in animal models of disease. This allows researchers to assess the safety and efficacy of the treatment before moving on to human clinical trials.
4) They can provide insights into disease mechanisms: Studying disease models in animals can provide valuable insights into the underlying mechanisms of a particular disease. This information can then be used to develop new treatments or improve existing ones.
5) Reduces the need for human testing: Using animal disease models reduces the need for human testing, which can be time-consuming, expensive, and ethically challenging. However, it is important to note that animal models are not perfect substitutes for human subjects, and results obtained from animal studies may not always translate to humans.
6) They can be used to study infectious diseases: Animal disease models can be used to study infectious diseases such as HIV, TB, and malaria. These models allow researchers to understand how the disease is transmitted, how it progresses, and how it responds to treatment.
7) They can be used to study complex diseases: Animal disease models can be used to study complex diseases such as cancer, diabetes, and heart disease. These models allow researchers to understand the underlying mechanisms of the disease and test potential treatments.
8) They are cost-effective: Animal disease models are often less expensive than human clinical trials, making them a cost-effective way to conduct research.
9) They can be used to study drug delivery: Animal disease models can be used to study drug delivery and pharmacokinetics, which is important for developing new drugs and drug delivery systems.
10) They can be used to study aging: Animal disease models can be used to study the aging process and age-related diseases such as Alzheimer's and Parkinson's. This allows researchers to understand how aging contributes to disease and develop potential treatments.
Neoplasm refers to an abnormal growth of cells that can be benign (non-cancerous) or malignant (cancerous). Neoplasms can occur in any part of the body and can affect various organs and tissues. The term "neoplasm" is often used interchangeably with "tumor," but while all tumors are neoplasms, not all neoplasms are tumors.
Types of Neoplasms
There are many different types of neoplasms, including:
1. Carcinomas: These are malignant tumors that arise in the epithelial cells lining organs and glands. Examples include breast cancer, lung cancer, and colon cancer.
2. Sarcomas: These are malignant tumors that arise in connective tissue, such as bone, cartilage, and fat. Examples include osteosarcoma (bone cancer) and soft tissue sarcoma.
3. Lymphomas: These are cancers of the immune system, specifically affecting the lymph nodes and other lymphoid tissues. Examples include Hodgkin lymphoma and non-Hodgkin lymphoma.
4. Leukemias: These are cancers of the blood and bone marrow that affect the white blood cells. Examples include acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL).
5. Melanomas: These are malignant tumors that arise in the pigment-producing cells called melanocytes. Examples include skin melanoma and eye melanoma.
Causes and Risk Factors of Neoplasms
The exact causes of neoplasms are not fully understood, but there are several known risk factors that can increase the likelihood of developing a neoplasm. These include:
1. Genetic predisposition: Some people may be born with genetic mutations that increase their risk of developing certain types of neoplasms.
2. Environmental factors: Exposure to certain environmental toxins, such as radiation and certain chemicals, can increase the risk of developing a neoplasm.
3. Infection: Some neoplasms are caused by viruses or bacteria. For example, human papillomavirus (HPV) is a common cause of cervical cancer.
4. Lifestyle factors: Factors such as smoking, excessive alcohol consumption, and a poor diet can increase the risk of developing certain types of neoplasms.
5. Family history: A person's risk of developing a neoplasm may be higher if they have a family history of the condition.
Signs and Symptoms of Neoplasms
The signs and symptoms of neoplasms can vary depending on the type of cancer and where it is located in the body. Some common signs and symptoms include:
1. Unusual lumps or swelling
4. Weight loss
5. Change in bowel or bladder habits
6. Unexplained bleeding
7. Coughing up blood
8. Hoarseness or a persistent cough
9. Changes in appetite or digestion
10. Skin changes, such as a new mole or a change in the size or color of an existing mole.
Diagnosis and Treatment of Neoplasms
The diagnosis of a neoplasm usually involves a combination of physical examination, imaging tests (such as X-rays, CT scans, or MRI scans), and biopsy. A biopsy involves removing a small sample of tissue from the suspected tumor and examining it under a microscope for cancer cells.
The treatment of neoplasms depends on the type, size, location, and stage of the cancer, as well as the patient's overall health. Some common treatments include:
1. Surgery: Removing the tumor and surrounding tissue can be an effective way to treat many types of cancer.
2. Chemotherapy: Using drugs to kill cancer cells can be effective for some types of cancer, especially if the cancer has spread to other parts of the body.
3. Radiation therapy: Using high-energy radiation to kill cancer cells can be effective for some types of cancer, especially if the cancer is located in a specific area of the body.
4. Immunotherapy: Boosting the body's immune system to fight cancer can be an effective treatment for some types of cancer.
5. Targeted therapy: Using drugs or other substances to target specific molecules on cancer cells can be an effective treatment for some types of cancer.
Prevention of Neoplasms
While it is not always possible to prevent neoplasms, there are several steps that can reduce the risk of developing cancer. These include:
1. Avoiding exposure to known carcinogens (such as tobacco smoke and radiation)
2. Maintaining a healthy diet and lifestyle
3. Getting regular exercise
4. Not smoking or using tobacco products
5. Limiting alcohol consumption
6. Getting vaccinated against certain viruses that are associated with cancer (such as human papillomavirus, or HPV)
7. Participating in screening programs for early detection of cancer (such as mammograms for breast cancer and colonoscopies for colon cancer)
8. Avoiding excessive exposure to sunlight and using protective measures such as sunscreen and hats to prevent skin cancer.
It's important to note that not all cancers can be prevented, and some may be caused by factors that are not yet understood or cannot be controlled. However, by taking these steps, individuals can reduce their risk of developing cancer and improve their overall health and well-being.
There are several types of lung neoplasms, including:
1. Adenocarcinoma: This is the most common type of lung cancer, accounting for approximately 40% of all lung cancers. It is a malignant tumor that originates in the glands of the respiratory tract and can be found in any part of the lung.
2. Squamous cell carcinoma: This type of lung cancer accounts for approximately 25% of all lung cancers and is more common in men than women. It is a malignant tumor that originates in the squamous cells lining the airways of the lungs.
3. Small cell lung cancer (SCLC): This is a highly aggressive form of lung cancer that accounts for approximately 15% of all lung cancers. It is often found in the central parts of the lungs and can spread quickly to other parts of the body.
4. Large cell carcinoma: This is a rare type of lung cancer that accounts for only about 5% of all lung cancers. It is a malignant tumor that originates in the large cells of the respiratory tract and can be found in any part of the lung.
5. Bronchioalveolar carcinoma (BAC): This is a rare type of lung cancer that originates in the cells lining the airways and alveoli of the lungs. It is more common in women than men and tends to affect older individuals.
6. Lymphangioleiomyomatosis (LAM): This is a rare, progressive, and often fatal lung disease that primarily affects women of childbearing age. It is characterized by the growth of smooth muscle-like cells in the lungs and can lead to cysts, lung collapse, and respiratory failure.
7. Hamartoma: This is a benign tumor that originates in the tissue of the lungs and is usually found in children. It is characterized by an overgrowth of normal lung tissue and can be treated with surgery.
8. Secondary lung cancer: This type of cancer occurs when cancer cells from another part of the body spread to the lungs through the bloodstream or lymphatic system. It is more common in people who have a history of smoking or exposure to other carcinogens.
9. Metastatic cancer: This type of cancer occurs when cancer cells from another part of the body spread to the lungs through the bloodstream or lymphatic system. It is more common in people who have a history of smoking or exposure to other carcinogens.
10. Mesothelioma: This is a rare and aggressive form of cancer that originates in the lining of the lungs or abdomen. It is caused by asbestos exposure and can be treated with surgery, chemotherapy, and radiation therapy.
Lung diseases can also be classified based on their cause, such as:
1. Infectious diseases: These are caused by bacteria, viruses, or other microorganisms and can include pneumonia, tuberculosis, and bronchitis.
2. Autoimmune diseases: These are caused by an overactive immune system and can include conditions such as sarcoidosis and idiopathic pulmonary fibrosis.
3. Genetic diseases: These are caused by inherited mutations in genes that affect the lungs and can include cystic fibrosis and primary ciliary dyskinesia.
4. Environmental diseases: These are caused by exposure to harmful substances such as tobacco smoke, air pollution, and asbestos.
5. Radiological diseases: These are caused by exposure to ionizing radiation and can include conditions such as radiographic breast cancer and lung cancer.
6. Vascular diseases: These are caused by problems with the blood vessels in the lungs and can include conditions such as pulmonary embolism and pulmonary hypertension.
7. Tumors: These can be benign or malignant and can include conditions such as lung metastases and lung cancer.
8. Trauma: This can include injuries to the chest or lungs caused by accidents or other forms of trauma.
9. Congenital diseases: These are present at birth and can include conditions such as bronchopulmonary foregut malformations and congenital cystic adenomatoid malformation.
Each type of lung disease has its own set of symptoms, diagnosis, and treatment options. It is important to seek medical attention if you experience any persistent or severe respiratory symptoms, as early diagnosis and treatment can improve outcomes and quality of life.
The prognosis for mantle-cell lymphoma is generally poor, with a five-year survival rate of approximately 40%. Treatment options include chemotherapy, immunotherapy, and autologous stem-cell transplantation. The disease often recurs after initial therapy, and subsequent treatments may be less effective.
Mantle-cell lymphoma can be difficult to distinguish from other types of non-Hodgkin lymphoma, such as follicular lymphoma or diffuse large B-cell lymphoma, and a correct diagnosis is important for determining appropriate treatment.
Slide: Mantle Cell Lymphoma (Image courtesy of Nephron/Wikimedia Commons)
1. Tumor size and location: Larger tumors that have spread to nearby tissues or organs are generally considered more invasive than smaller tumors that are confined to the original site.
2. Cellular growth patterns: The way in which cancer cells grow and divide can also contribute to the overall invasiveness of a neoplasm. For example, cells that grow in a disorganized or chaotic manner may be more likely to invade surrounding tissues.
3. Mitotic index: The mitotic index is a measure of how quickly the cancer cells are dividing. A higher mitotic index is generally associated with more aggressive and invasive cancers.
4. Necrosis: Necrosis, or the death of cells, can be an indication of the level of invasiveness of a neoplasm. The presence of significant necrosis in a tumor is often a sign that the cancer has invaded surrounding tissues and organs.
5. Lymphovascular invasion: Cancer cells that have invaded lymphatic vessels or blood vessels are considered more invasive than those that have not.
6. Perineural invasion: Cancer cells that have invaded nerve fibers are also considered more invasive.
7. Histological grade: The histological grade of a neoplasm is a measure of how abnormal the cancer cells look under a microscope. Higher-grade cancers are generally considered more aggressive and invasive than lower-grade cancers.
8. Immunohistochemical markers: Certain immunohistochemical markers, such as Ki-67, can be used to evaluate the proliferative activity of cancer cells. Higher levels of these markers are generally associated with more aggressive and invasive cancers.
Overall, the degree of neoplasm invasiveness is an important factor in determining the likelihood of the cancer spreading to other parts of the body (metastasizing) and in determining the appropriate treatment strategy for the patient.
There are several types of colonic neoplasms, including:
1. Adenomas: These are benign growths that are usually precursors to colorectal cancer.
2. Carcinomas: These are malignant tumors that arise from the epithelial lining of the colon.
3. Sarcomas: These are rare malignant tumors that arise from the connective tissue of the colon.
4. Lymphomas: These are cancers of the immune system that can affect the colon.
Colonic neoplasms can cause a variety of symptoms, including bleeding, abdominal pain, and changes in bowel habits. They are often diagnosed through a combination of medical imaging tests (such as colonoscopy or CT scan) and biopsy. Treatment for colonic neoplasms depends on the type and stage of the tumor, and may include surgery, chemotherapy, and/or radiation therapy.
Overall, colonic neoplasms are a common condition that can have serious consequences if left untreated. It is important for individuals to be aware of their risk factors and to undergo regular screening for colon cancer to help detect and treat any abnormal growths or tumors in the colon.
Malignant prostatic neoplasms are cancerous tumors that can be aggressive and spread to other parts of the body (metastasize). The most common type of malignant prostatic neoplasm is adenocarcinoma of the prostate, which accounts for approximately 95% of all prostate cancers. Other types of malignant prostatic neoplasms include sarcomas and small cell carcinomas.
Prostatic neoplasms can be diagnosed through a variety of tests such as digital rectal examination (DRE), prostate-specific antigen (PSA) test, imaging studies (ultrasound, CT scan or MRI), and biopsy. Treatment options for prostatic neoplasms depend on the type, stage, and grade of the tumor, as well as the patient's age and overall health. Treatment options can include active surveillance, surgery (robotic-assisted laparoscopic prostatectomy or open prostatectomy), radiation therapy (external beam radiation therapy or brachytherapy), and hormone therapy.
In summary, Prostatic Neoplasms are tumors that occur in the prostate gland, which can be benign or malignant. The most common types of malignant prostatic neoplasms are adenocarcinoma of the prostate, and other types include sarcomas and small cell carcinomas. Diagnosis is done through a variety of tests, and treatment options depend on the type, stage, and grade of the tumor, as well as the patient's age and overall health.
SCC typically appears as a firm, flat, or raised bump on the skin, and may be pink, red, or scaly. The cancer cells are usually well-differentiated, meaning they resemble normal squamous cells, but they can grow rapidly and invade surrounding tissues if left untreated.
SCC is more common in fair-skinned individuals and those who spend a lot of time in the sun, as UV radiation can damage the skin cells and increase the risk of cancer. The cancer can also spread to other parts of the body, such as lymph nodes or organs, and can be life-threatening if not treated promptly and effectively.
Treatment for SCC usually involves surgery to remove the cancerous tissue, and may also include radiation therapy or chemotherapy to kill any remaining cancer cells. Early detection and treatment are important to improve outcomes for patients with SCC.
Adenocarcinoma is a term used to describe a variety of different types of cancer that arise in glandular tissue, including:
1. Colorectal adenocarcinoma (cancer of the colon or rectum)
2. Breast adenocarcinoma (cancer of the breast)
3. Prostate adenocarcinoma (cancer of the prostate gland)
4. Pancreatic adenocarcinoma (cancer of the pancreas)
5. Lung adenocarcinoma (cancer of the lung)
6. Thyroid adenocarcinoma (cancer of the thyroid gland)
7. Skin adenocarcinoma (cancer of the skin)
The symptoms of adenocarcinoma depend on the location of the cancer and can include:
1. Blood in the stool or urine
2. Abdominal pain or discomfort
3. Changes in bowel habits
4. Unusual vaginal bleeding (in the case of endometrial adenocarcinoma)
5. A lump or thickening in the breast or elsewhere
6. Weight loss
8. Coughing up blood (in the case of lung adenocarcinoma)
The diagnosis of adenocarcinoma is typically made through a combination of imaging tests, such as CT scans, MRI scans, and PET scans, and a biopsy, which involves removing a sample of tissue from the affected area and examining it under a microscope for cancer cells.
Treatment options for adenocarcinoma depend on the location of the cancer and can include:
1. Surgery to remove the tumor
2. Chemotherapy, which involves using drugs to kill cancer cells
3. Radiation therapy, which involves using high-energy X-rays or other particles to kill cancer cells
4. Targeted therapy, which involves using drugs that target specific molecules on cancer cells to kill them
5. Immunotherapy, which involves using drugs that stimulate the immune system to fight cancer cells.
The prognosis for adenocarcinoma is generally good if the cancer is detected and treated early, but it can be more challenging to treat if the cancer has spread to other parts of the body.
Cyclin-dependent kinase 9
Cyclin-dependent kinase 1
Cyclin-dependent kinase 10
Cyclin-dependent kinase 6
Cyclin-dependent kinase 2
Cyclin-dependent kinase 7
Cyclin-dependent kinase 4
Cyclin-dependent kinase 3
Cyclin-dependent kinase 8
Cyclin-dependent kinase inhibitor 1C
Cyclin-dependent kinase complex
Epstein-Barr virus nuclear antigen 2
List of MeSH codes (D12.776.930)
List of MeSH codes (D12.776)
AP-1 transcription factor
Index of biochemistry articles
Transcription factor II B
G2-M DNA damage checkpoint
Targeting cyclin-dependent kinase 9 in cancer therapy - PubMed
Cyclin-dependent Kinase 9 as a Potential Target for Anti-TNF-resistant Inflammatory Bowel Disease. | Cell Mol Gastroenterol...
Superenhancers as master gene regulators and novel therapeutic targets in brain tumors | Experimental & Molecular Medicine
DeCS 2006 - Changed terms
RNA glycosidase and other agents target Tat to inhibit HIV-1 transcription - PubMed
CDK9/CCNT1 (Human) Recombinant Protein - (P4664) - Products - Abnova
Synthesis and application of functionally diverse 2,6,9-trisubstituted purine libraries as CDK inhibitors - PubMed
Cyclin-Dependent Kinase 2 | Harvard Catalyst Profiles | Harvard Catalyst
Targeted Therapy | CancerQuest
Purvalanol B | ≥99%(HPLC) | CDK inhibitor | AdooQ®
GSE9006 HEALTHY VS TYPE 1 DIABETES PBMC AT DX DN
Home - Dr Manikandan Periyasamy
CDKL5 gene: MedlinePlus Genetics
Ashok Kulkarni, Ph.D. | National Institute of Dental and Craniofacial Research
Pharos : Target Details - CDK9
Novel Targeting of Transcription and Metabolism in Glioblastoma | NIH Research Festival
Pharos : Ligand List
Jayson Jay - Publications - UTMB Health Research Expert Profiles
University of Glasgow - Schools - School of Cancer Sciences - Our staff - Dr Alison M Michie
NCIt Preferred Name NCIt code Swiss Prot
- This is a Phase 1 dose-escalation and confirmation study of PRT2527, a Cyclin-dependent Kinase 9 (CDK9) inhibitor, in participants with advanced solid tumors. (clinicaltrials.gov)
- 13. Flavopiridol: the first cyclin-dependent kinase inhibitor in human clinical trials. (nih.gov)
- 16. Flavopiridol, a novel cyclin-dependent kinase inhibitor, in clinical development. (nih.gov)
- Purvalanol B is a cyclin-dependent kinase inhibitor. (adooq.com)
- CGP60474 is a potent inhibitor of cyclin-dependent kinase (CDK). (adooq.com)
- TG003 is a potent, specific, reversible, and ATP competitive inhibitor of Cdc2 like kinase(Clk). (adooq.com)
- TG02 is a multi-kinase inhibitor, mainly inhibiting cyclin-dependent kinase 9 (CDK9), thus diminishing RNA polymerase II activation to suppress the expressions of anti-apoptotic proteins such as Mcl-1and Survivin. (nih.gov)
- Gene polymorphisms of cyclin-dependent kinase inhibitor and matrix metalloproteinase-9 in Sudanese patients with esophageal squamous cell carcinoma. (cdc.gov)
- E2F-6: a novel member of the E2F family is an inhibitor of E2F-dependent transcription. (nih.gov)
- Moreover, pretreatment of cells with curcumin, an activation of AP-1 (activator protein-1) inhibitor, inhibited silica -induced cell cycle alteration, the decreased expression of E2F-4 and overexpression of cyclin D1 and CDK4. (cdc.gov)
- In this study, we evaluate the effect of targeting the transactivation function of T-bet using inhibitors of P-TEFb (CDK9- cyclin T ), a transcriptional elongation factor downstream of T-bet. (bvsalud.org)
- Using an adaptive immune-mediated colitis model, human colonic lymphocytes from patients with IBD and multiple large clinical datasets, we investigate the effect of cyclin-dependent kinase 9 (CDK9) inhibitors on cytokine production and gene expression in colonic CD4+ T cells and link these genetic modules to clinical response in patients with IBD. (bvsalud.org)
- 1. Inhibitors of cyclin-dependent kinase modulators for cancer therapy. (nih.gov)
- 15. Dual action of the inhibitors of cyclin-dependent kinases: targeting of the cell-cycle progression and activation of wild-type p53 protein. (nih.gov)
- 17. [Research on cyclin-dependent kinase inhibitors: state of the art and perspective]. (nih.gov)
- 18. The use of cyclin-dependent kinase inhibitors alone or in combination with established cytotoxic drugs in cancer chemotherapy. (nih.gov)
- 20. Cyclin-dependent kinase inhibitors. (nih.gov)
- Alternatively, the activity of kinases can be inhibited by chemical inhibitors of varying specificity [ 5 ]. (oncotarget.com)
- Synthesis and Structure-Activity relationships of cyclin-dependent kinase 11 inhibitors based on a diaminothiazole scaffold. (harvard.edu)
- Probing the catalytic functions of Bub1 kinase using the small molecule inhibitors BAY-320 and BAY-524. (unibas.ch)
- While there are hundreds of kinases, only three amino acids, serine, threonine, and tyrosine, undergo modification by kinases in eukaryotes [ 2 ]. (oncotarget.com)
- 6. Small molecule modulators of cyclin-dependent kinases for cancer therapy. (nih.gov)
- 9. Small-molecule cyclin-dependent kinase modulators. (nih.gov)
- 10. Novel small molecule cyclin-dependent kinases modulators in human clinical trials. (nih.gov)
- This is the third announcement from AstraZeneca this side of the New Year focusing on oncology, after a preclinical partnership with Horizon and the acquisition of a small molecule cyclin-dependent kinase 9 (CDK9) programme to target cancer cells. (biopharma-reporter.com)
- Transcriptional cyclin-dependent kinases regulate all phases of transcription. (oncotarget.com)
- A multifunctional CDC2 kinase-related kinase that plays roles in transcriptional elongation, CELL DIFFERENTIATION , and APOPTOSIS . (nih.gov)
- Unlike traditional cyclins, which regulate the CELL CYCLE, type T cyclins appear to regulate transcription and are components of positive transcriptional elongation factor B. (bvsalud.org)
- Tumor necrosis factor-alpha regulates cyclin-dependent kinase 5 activity during pain signaling through transcriptional activation of p35. (nih.gov)
- Human myt1 is a cell cycle-regulated kinase that inhibits cdc2 but not cdk2 activity. (nih.gov)
- Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. (abnova.com)
- Cyclins Cln1-3 are triggers for G1 and G1/S, while among B-type cyclins Clb5 and Clb6 drive S phase, Clb3 and Clb4 are specific for early mitotic events, and Clb1 and Clb2 complete the progression to mitosis. (eu.org)
- Spt5 is phosphorylated within its C-terminal domain (CTD) by cyclin-dependent kinase 9 (Cdk9), catalytic component of positive transcription elongation factor b (P-TEFb). (inrs.ca)
- Cyclin-dependent kinase 2 (CDK2) is a kinase involved in the regulation of cell cycle, being responsible for triggering DNA synthesis. (unito.it)
- The protein encoded by this gene is a member of the cyclin-dependent protein kinase (CDK) family. (abnova.com)
- The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. (abnova.com)
- A miR-151 binding site polymorphism in the 3'-untranslated region of the cyclin E1 gene associated with nasopharyngeal carcinoma. (cdc.gov)
- This kinase was found to be a component of the multiprotein complex TAK/P-TEFb, which is an elongation factor for RNA polymerase II-directed transcription and functions by phosphorylating the C-terminal domain of the largest subunit of RNA polymerase II. (abnova.com)
- This cyclin tightly associates with CDK9 kinase, and was found to be a major subunit of the transcription elongation factor p-TEFb. (abnova.com)
- The kinase complex containing this cyclin and the elongation factor can interact with, and act as a cofactor of human immunodeficiency virus type 1 (HIV-1) Tat protein, and was shown to be both necessary and sufficient for full activation of viral transcription. (abnova.com)
- Member of the cyclin-dependent kinase pair (CDK9/cyclin-T) complex, also called positive transcription elongation factor b (P-TEFb), which facilitates the transition from abortive to productive elongation by phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A, SUPT5H and RDBP. (nih.gov)
- Since Spt5 is a unique target of Cdk9, and Rtf1 is the only known pSpt5-binding factor, the Plus3/pSpt5 interaction is thought to be a key Cdk9-dependent event regulating RNAPII elongation. (inrs.ca)
- Our results elucidate unexpected complexity underlying Cdk9-dependent pathways that regulate transcription elongation. (inrs.ca)
- Given the large number of kinases and their limited specificity, protein phosphorylation apparently undergoes several layers of regulation. (oncotarget.com)
- Recruitment of kinases and control of their activity substantially contribute to the regulation of protein phosphorylation in vivo [ 4 ]. (oncotarget.com)
- The question of the number of kinases that can participate in phosphorylation of a target site in vivo is difficult to answer. (oncotarget.com)
- This cyclin and its kinase partner were also found to be involved in the phosphorylation and regulation of the carboxy-terminal domain (CTD) of the largest RNA polymerase II subunit. (abnova.com)
- Cyclin-dependent kinase 5 modulates nociceptive signaling through direct phosphorylation of transient receptor potential vanilloid 1. (nih.gov)
- Cyclin-dependent kinases (Cdks) coordinate hundreds of molecular events during the cell cycle via Ser/Thr phosphorylation. (eu.org)
- Docking motifs control the timing of cell cycle events by enabling preferential interaction and phosphorylation of substrates by a specific cyclin/Cdk complex. (eu.org)
- Inhibition of DNA binding by the phosphorylation of poly ADP-ribose polymerase protein catalysed by protein kinase C. Biochem Biophys Res Commun 187 , 730-736. (nih.gov)
- Activation of the ATM kinase by ionizing radiation and phosphorylation of p53. (nih.gov)
- Roles of the ERK, JNK/AP-1/cyclin D1-CDK4 pathway in silica -induced cell cycle changes in human embryo lung fibroblast cells. (cdc.gov)
- The cell cycle alternations were accompanied with overexpression of cyclin D1 and CDK4 (cyclin-dependent kinase 4) in a time-dependent manner. (cdc.gov)
- Furthermore, both antisense cyclin D1 and antisense CDK4 can block silica -induced cell cycle changes. (cdc.gov)
- These results suggest that silica exposure can induce cell cycle changes, which may be mediated through ERK, JNK/AP-1/cyclin D1-CDK4-dependent pathway. (cdc.gov)
- Kinases are enzymes that add phosphate groups onto proteins. (cancerquest.org)
- The CDKL5 protein acts as a kinase, which is an enzyme that changes the activity of other proteins by adding a cluster of oxygen and phosphorus atoms (a phosphate group) at specific positions. (medlineplus.gov)
- Mutations in the kinase domain disrupt the ability of CDKL5 to add phosphate groups to other proteins. (medlineplus.gov)
- Cyclins use the conserved hydrophobic pocket (hp) to bind docking motifs on partner proteins. (eu.org)
Implicated in the regulation1
- Cyclin-dependent kinase 9 (CDK9) has been implicated in the regulation of promoter-proximal pausing of RNA polymerase II and more recently in transcription termination. (oncotarget.com)
- SEs are susceptible to inhibition by their key components, such as bromodomain protein 4 and cyclin-dependent kinase 7, providing new opportunities for antitumor therapy. (nature.com)
- Here we analyzed the cellular phosphoproteome upon inhibition of CDK9 by combining analog-sensitive kinase technology with quantitative phosphoproteomics in Raji B-cells. (oncotarget.com)
- Pharmacological inhibition of Polo-like kinase 1 (PLK1) by BI-2536 decreases the viability and survival of hamartin and tuberin deficient cells via induction of apoptosis and attenuation of autophagy. (uc.edu)
- With cell cycle progression, different cyclins bind to Cdks to control their function by providing docking sites for substrates and also by modulating Cdk active site specificity. (eu.org)
- The sequential attachment of different cyclins to Cdks represents the periodic driving force that ensures a controlled progression through the cell cycle. (eu.org)
- These polymorphically expressed genes may be positively (or inversely) associated with susceptibility to cancer and several other diseases because of their important role in the detoxification (or activation) of xenobiotics and environmental chemicals (9, 10). (cdc.gov)
- Doxorubicin induces cardiomyocyte apoptosis and atrophy through cyclin-dependent kinase 2-mediated activation of forkhead box O1. (harvard.edu)
- Activation of cyclin-dependent 5 mediates orofacial mechanical hyperalgesia. (nih.gov)
- This protein forms a complex with and is regulated by its regulatory subunit cyclin T or cyclin K. HIV-1 Tat protein was found to interact with this protein and cyclin T, which suggested a possible involvement of this protein in AIDS. (abnova.com)
- Here a single Cdk, Cdk1, associates with different cyclins to mediate all major cell cycle transitions. (eu.org)
- Additionally, quercetin limited aHSC proliferation by inducing a G1 arrest as evidenced by decreased expression of cyclin D1、D2、A、B1、E. Moreover quercetin and gallic acid induced aHSC apoptosis via Fas/Fas ligand-mediated extrinsic pathway. (ncl.edu.tw)
- Recently, several studies have reported that based on their biological activities, lncRNAs are highly associated with various diseases including cancer [ 9 , 10 ]. (genominfo.org)
- Cyclins may use additional surfaces to dock substrates, as with the mammalian Cyclin D-specific ( DOC_CYCLIN_D_Helix_1 ) and the budding yeast Cln2-specific leucine- and proline-rich LP ( DOC_CYCLIN_yCln2_LP_2 ) motifs. (eu.org)
- aurora kinase A [Source:HGNC Symbol;Ac. (gsea-msigdb.org)
- TG02-induced cytotoxicity was blocked by the overexpression of phosphorylated CDK9, suggesting a CDK9-dependent cell killing. (nih.gov)
- These changes were blocked by overexpression of dominant-negative mutants of ERK (extracellular signal-regulated protein kinase) or the JNK (stress-activated c-Jun NH(2)-terminal kinase), respectively. (cdc.gov)
- Cyclin-dependent kinases (Cdks) are central regulatory enzymes of the eukaryotic cell cycle. (eu.org)
- Estrogen activates pyruvate kinase M2 and increases the growth of TSC2-deficient cells. (uc.edu)
- 3. Cyclin-dependent kinase modulators: a novel class of cell cycle regulators for cancer therapy. (nih.gov)
- 11. Drugging cell cycle kinases in cancer therapy. (nih.gov)
- Treatment of aHSCs with quercetin and gallic acid inhibited cell viability in a dose- and time-dependent manner. (ncl.edu.tw)
- Matrix metalloproteinase-9 polymorphisms and renal cell carcinoma in a Japanese population. (cdc.gov)
- Matrix metalloproteinase 1, 3, and 9 polymorphisms and esophageal squamous cell carcinoma risk. (cdc.gov)
- Cyclin-Dependent Kinase 2" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (harvard.edu)
- 7. Development of cyclin-dependent kinase modulators as novel therapeutic approaches for hematological malignancies. (nih.gov)
- Recruitment of p300/CBP in p53-dependent signal pathways. (nih.gov)
- Cyclin-dependent Kinase 9 as a Potential Target for Anti-TNF-resistant Inflammatory Bowel Disease. (bvsalud.org)
- Kinases can be removed by genetic knockout or by RNA interference-mediated downregulation. (oncotarget.com)
- This type of mutation occurs most often in a region of the protein called the kinase domain, which is essential for the protein's kinase function. (medlineplus.gov)
- 4. Cyclin-dependent kinases as targets for cancer therapy. (nih.gov)
- A cyclin subtype that is found associated with CYCLIN-DEPENDENT KINASE 9. (bvsalud.org)
- It partners with CYCLIN E to regulate entry into S PHASE and also interacts with CYCLIN A to phosphorylate RETINOBLASTOMA PROTEIN. (harvard.edu)