P53 dna. Medical search. Frequent questions

TP53 gene encodes proteins that bind to DNA and regulate gene expression to prevent mutations of the genome. (wikipedia.org)
Our structural and biophysical data provide compelling evidence for the mechanism of rescue of mutant p53 by intragenic suppressor mutations and reveal features by which proteins can adapt to deleterious mutations. (rcsb.org)
Our recent report indicated that tumor suppressor gene ( p53 ) mutations and protein aberrant expression were detected in pterygium. (molvis.org)
Hepatocellular carcinoma (HCC) is a deadly cancer, with the dominant driver mutations such as p53 yet undruggable. (authorea.com)
If p53 is inactivated, as it is in over half of all human cancers, checks and balances on cell growth fail to operate, and body cells start to accumulate mutations, which ultimately may lead to cancer. (news-medical.net)
Cancer is caused by genetic changes, or DNA mutations, that allow cells to grow and divide uncontrollably. (nih.gov)
The majority of classical LFS families harbour germline mutations of the p53 tumour suppressor gene. (bmj.com)
These had all been previously screened for the presence of p53 mutations in exons 2 and 4-11 by single strand conformational polymorphism (SSCP) analysis and DNA sequencing as previously described. (bmj.com)
Cancers occur when genetic mutations build up in critical genes, specifically those that control cell growth and division (proliferation) or the repair of damaged DNA. (medlineplus.gov)
TP53 gene mutations result in the production of an altered p53 protein that cannot bind to DNA. (medlineplus.gov)
Researchers irradiated stem cells from mouse embryos to cause genetic mutations, then stained the cells to reveal the tumour suppressing protein p53. (newscientist.com)
Rothmund-Thomson syndrome (poikiloderma congenitale) has been attributed to mutations of the RECQL4 gene on 8q24, which encodes a RecQ DNA helicase. (medscape.com)
Point mutations in K-ras and p53 were studied by PCR restriction fragment length polymorphism analysis and DNA sequencing. (cdc.gov)
There were no point mutations observed in codons 12, 13, and 61 of K-ras or in exons 4-10 of p53 and no observed differences in the levels of any of the proteins studied. (cdc.gov)
Germline mutations in the p53 tumor suppressor gene are associated with the Li-Fraumeni syndrome, characterized by childhood sarcoma, leukemia and early onset breast cancer and has occasionally been found also in familial breast-ovarian cancer. (lu.se)

The DNA damage response (DDR) is a mechanism that protects cells against radiation-induced oxidative DNA damage by causing cell cycle arrest and apoptosis. (researchsquare.com)
Ionizing radiation is well known to induce oxidative DNA damage, such as DNA double-strand breaks (DSBs), and consequently trigger the DNA damage response (DDR), including cell cycle arrest and apoptosis. (researchsquare.com)
p53 plays a role in regulation or progression through the cell cycle, apoptosis, and genomic stability by means of several mechanisms: It can activate DNA repair proteins when DNA has sustained damage. (wikipedia.org)
It can initiate apoptosis (i.e., programmed cell death) if DNA damage proves to be irreparable. (wikipedia.org)
The tumor suppressor p53 regulates different cellular pathways involved in cell survival, DNA repair, apoptosis, and senescence. (uni-konstanz.de)
Although the conventional activities of p53 such as cell cycle arrest, senescence, and apoptosis are well accepted as the major checkpoints in stress responses, accumulating evidence implicates the importance of other tumor suppression mechanisms. (nature.com)
Is p53-dependent ferroptosis sufficient for tumor suppression in the absence of cell cycle arrest, senescence, and apoptosis? (nature.com)
To date, various mechanisms have been suggested to explain the powerful tumor-suppressive effect of p53, including the induction of cell cycle arrest, senescence, and apoptosis. (nature.com)
It initiates the process of programmed cell death, or apoptosis, which directs the cell to commit suicide, permanently removing the damaged DNA from the organism. (news-medical.net)
Instead of accumulating in mouse cells and halting cell division in the genetically engineered mice, the altered p53 protein performed flawlessly: it was unstable when no DNA damage was present and was stable and fully functional when needed to halt the cycle cell to repair DNA damage or to induce apoptosis. (news-medical.net)
Functional assays comparing elephant and human cells showed that in response to DNA damage, cells from elephants had higher cell death (apoptosis) rates but didn't boost DNA repair mechanisms. (nih.gov)
These results suggest that elephants may have evolved to resist cancer by triggering apoptosis through p53 to efficiently remove mutant cells. (nih.gov)
Expression of the p53 target CDIP correlates with sensitivity to TNFα-induced apoptosis in cancer cells. (nih.gov)
If the damage is not repaired on time, the activation of p53 results in programmed cell death known as apoptosis. (scienceblog.com)
When DNA becomes damaged, p53 helps determine whether the DNA will be repaired or the cell will self-destruct ( undergo apoptosis ). (medlineplus.gov)
In addition to the pathogonomic translocation , MCL progression is controlled by secondary genetic abberations and dysregulated signaling pathways involved in DNA damage repair , proliferation , and apoptosis . (wikidoc.org)
p53 is a transcription factor that participates in cell cycle checkpoint processes and apoptosis. (lu.se)

We studied p53 phospho-profiles induced by DNA-damaging agents (fludarabine, doxorubicin) in 71 TP53-intact primary CLL samples. (muni.cz)
Profile II samples were less capable of activating p53 target genes upon doxorubicin exposure, resembling TP53-mutant samples at the transcriptomic level, whereas standard p53 signaling was triggered in profile I. ATM locus defects were more common in profile II. (muni.cz)
The samples also differed in the basal activity of the hypoxia pathway: the highest level was detected in TP53-mutant samples, followed by profile II and profile I. Our study suggests that wild-type TP53 CLL cells with less phosphorylated p53 show TP53-mutant-like behavior after DNA damage. (muni.cz)
The tumor suppressor TP53 (also called p53) has been among the most extensively studied genes since its discovery in 1979 [ 1 , 2 ]. (nature.com)
TP53 codes for the protein p53, a crucial tumor suppressor that stops cells with damaged DNA from dividing. (nih.gov)
The TP53 gene provides instructions for making a protein, called p53, that is located in the nucleus of cells throughout the body, where it attaches (binds) directly to DNA. (medlineplus.gov)

ΔNp63α has been reported to transcriptionally inhibit the tumour suppression protein p53. (researchsquare.com)
The DNA guardian protein p53 plays the most important role in DDR: it promotes DNA repair and the elimination of cells that are unable to repair the damage caused by oxidative stresses, including radiation. (researchsquare.com)
p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. (wikipedia.org)

As such, p53 has been described as "the guardian of the genome" because of its role in conserving stability by preventing genome mutation. (wikipedia.org)
Mutation of the p53 gene is a critical event in the elaboration of many tumors of diverse origin. (mdanderson.org)
HPV 16/18 infection was detected by nested-polymerase chain reaction (nested-PCR), the p53 mutation was detected by direct sequencing, and the p53 and the HPV 16/18 E6 proteins were studied using immunohistochemistry on 129 pterygial specimens and 20 normal conjunctivas. (molvis.org)
In addition, p53 protein negative expression in pterygium was correlated with HPV16/18 E6 oncoprotein expression but not with a p53 mutation. (molvis.org)
In this report, we analyzed p53 protein expression and gene mutation in pterygium in comparison with HPV 16/18 infection and E6 oncoprotein expression in pterygium tissues to understand whether the HPV infection was involved in pterygium pathogenesis. (molvis.org)
The family manifested no linkage to the p53 gene (a two-point LOD-score of -0.41), and has previously also been excluded for linkage to the BRCA1 and BRCA2 loci, as well as being carrier of a BRCA1 germline mutation. (lu.se)
Although it seems unlikely that the p53 germline mutation is the major cause of disease predisposition in Lund 5, the data suggest that some p53 alteration may confer a subtle influence on breast cancer development and progression. (lu.se)
In about half of human cancers, p53 is inactivated through DNA mutation. (who.int)

After screening different histone lysine methyltransferases and demethylases, we identified JMJD2B/KDM4B as a p53-inducible gene in response to DNA damage. (escholarship.org)
The p53 protein is activated in response to DNA damage, serving as a checkpoint in the elimination or repair of cells with damaged DNA. (mdanderson.org)
Potential Mechanisms for Cancer Resistance in Elephants and Comparative Cellular Response to DNA Damage in Humans. (nih.gov)
Acts upstream of or within intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator and tumor necrosis factor-mediated signaling pathway. (nih.gov)

p53 hypophosphorylation and the related lower ability to respond to DNA damage are linked to ATM locus defects and the higher basal activity of the hypoxia pathway. (muni.cz)
Studies of human embryonic stem cells (hESCs) commonly describe the nonfunctional p53-p21 axis of the G1/S checkpoint pathway with subsequent relevance for cell cycle regulation and the DNA damage response (DDR). (wikipedia.org)
Alterations in components of the p53 pathway, such as amplification of the Mdm2 gene, which encodes a p53 inhibitor, also contribute to tumorigenesis. (mdanderson.org)
The overall goal of my laboratory is to understand the signals that regulate the p53 pathway and the consequences of expressing wild-type or mutant p53. (mdanderson.org)
Dr. Lozano is recognized as a pioneer in describing the p53 pathway, a recognized tumor suppressor gene associated with cancer. (mdanderson.org)
Guillermina's pioneering work in genetics has paved the way for innovative research at MD Anderson and at cancer centers around the world," said President Peter WT Pisters, M.D. "We are proud to count her among our most distinguished faculty, and we are excited to see her recognized by our peers for her transformative work in outlining the p53 pathway. (mdanderson.org)
Lozano has been elected to the National Academy of Sciences (NAS) for her pioneering work in describing the p53 pathway, a recognized tumor suppressor gene associated with cancer. (mdanderson.org)
Many chemotherapeutical drugs used to treat cancer exert their biological effects on tumor cells through activation of the p53 pathway. (news-medical.net)
The NHEJ pathway, which repairs double-strand breaks in DNA, is one of the major pathways in tumor cells that respond to radiation treatment and chemotherapeutic agents. (sciencedaily.com)
Inhibition of the NHEJ pathway has been proposed by oncology researchers to synergize DNA-damaging therapies for better treatment outcomes for TNBCs. (sciencedaily.com)
Collectively, our study provides new insight into the DNA damage repair pathway, long non-coding RNAs, and triple-negative breast cancer. (sciencedaily.com)
In response to DNA-damaging agents, the wild-type p53-activated fragment 1 (WAF1 also known as p21) is an important downstream effector in the p53-specific growth arrest pathway. (lu.se)

However, vast data from 30 years of further study indicate a tumor-suppressive role of p53 [ 1 , 3 ]. (nature.com)
The research describes for the first time the physiological role of p53 in the development of meiosis and suggests that the function of the tumour suppressor gene can be result of an evolution of primitive activities related with the progression of meiosis. (scienceblog.com)

Our results demonstrate that DNA-PKcs, unlike the related ATM protein, is not essential for the activation of p53 and G 1 cell cycle arrest in response to ionizing radiation. (uthscsa.edu)
Through the observation of genetically modified flies to determine the activation of p53, the team led by Dr John Abrams of the University of Texas Southwestern Medical Center and with the participation of Dr Ignasi Roig from the Cytology and Histology Unit of the Department of Cellular Biology, Physiology and Immunology at Universitat Autònoma de Barcelona, discovered that p53 becomes activated during the formation of gametes (spermatozoids and ova). (scienceblog.com)

A mutant p53 will no longer bind DNA in an effective way, and, as a consequence, the p21 protein will not be available to act as the "stop signal" for cell division. (wikipedia.org)
Moreover, an HDAC3 binding-deficient SMRT DAD mutant coactivated p53 transcriptional activity. (nih.gov)
The antibody should recognize human wild-type and mutant p53. (abcam.com)
Functionally, this increased stability of SCML2 enhances resistance to DNA damage agents in p53-positive, p53-mutant, and p53-negative cells. (lucmg.com)
In p53-mutant or p53-negative cancer cells, SCML2 promotes CHK1 and p21 stability by inhibiting their ubiquitination, thereby enhancing the resistance to DNA damage agents. (lucmg.com)
Ectopic or endogenous VCP stabilized p53-R273H by binding to MDM2 and disrupting its association with mutant p53. (aacrjournals.org)
Both p53 wild type and p53 mutant samples were included in the p16 INK4a analysis to determine whether germline alterations of one gene precluded the occurrence of alterations of the other. (bmj.com)

The p53 proteins (originally thought to be, and often spoken of as, a single protein) are crucial in vertebrates, where they prevent cancer formation. (wikipedia.org)
It can arrest growth by holding the cell cycle at the G1/S regulation point on DNA damage recognition-if it holds the cell here for long enough, the DNA repair proteins will have time to fix the damage and the cell will be allowed to continue the cell cycle. (wikipedia.org)
She also showed that common p53 mutants fail to launch transcription, and discovered other proteins, Mdm2 and Mdm4, which play critical roles in inhibiting p53 activity in development and cancer. (mdanderson.org)
Notably, Andro-induced p62 aggregation promoted proteasomal degradation of RAD51 and 53BP1, two essential proteins involved in DNA damage repair. (authorea.com)
To further examine whether the SUMO ligase activity of PIAS proteins is BGJ398 enzyme inhibitor restricted to p53, we tested several other SUMO targets in this system. (cancer-pictures.org)
When higher than normal levels of p53 tumor suppressor exist, there is enough p53 to bind to many regulatory sites in the cell's genome to activate the production of other proteins that will halt cell division if the DNA damage can be repaired. (news-medical.net)
Glass or quartz nanopipettes have found increasing use as tools for studying the biophysical properties of DNA and proteins, and as sensor devices. (imperial.ac.uk)
This molecule enhances the repair of DNA breaks by serving as a scaffold that links two other proteins in the repair machinery. (sciencedaily.com)
The two repair scaffold proteins, Ku80 and DNA-PKcs, that LINP1 links coordinate the non-homologous end-joining (NHEJ) repair molecules that fix double-strand breaks in DNA. (sciencedaily.com)
8 9 This lack of an absolute phenotype:genotype concordance could be attributed to incomplete screening of the p53 gene, inactivation of the p53 protein through interaction with other cellular proteins or viruses, or defects in other genes involved in p53 mediated cell cycle regulatory pathways. (bmj.com)
Six proto-oncogenes (K-ras, c-myc, c-fos, c-jun, c-sis, and erbB), as well as the p53 tumor suppressor, were investigated for gene amplification using differential polymerase chain reaction (PCR), while the expression of the proteins produced by these genes was evaluated by Western blot analysis. (cdc.gov)

The p53 tumor suppressor protein plays a critical role in orchestrating the genomic response to various stress signals by acting as a master transcriptional regulator. (escholarship.org)
JMJD2B induction attenuates the transcription of key p53 transcriptional targets including p21, PIG3 and PUMA, and this modulation is dependent on the catalytic capacity of JMJD2B. (escholarship.org)
These findings indicate that JMJD2B acts in an auto-regulatory loop by which p53, through JMJD2B activation, is able to influence its own transcriptional program. (escholarship.org)
The p21 gene contains several p53 response elements that mediate direct binding of the p53 protein, resulting in transcriptional activation of the gene encoding the p21 protein. (wikipedia.org)
In 1987, she became the first to establish p53 as a transcriptional activator of other genes. (mdanderson.org)
Here we compare transcriptional responses to physiological DNA breaks with responses to genotoxic DNA damage induced by ionizing radiation. (biomedcentral.com)
Comparing these transcriptional responses provides a greater understanding of the mechanisms cells use in the differentiation between types of DNA damage and the potential consequences of different sources of damage. (biomedcentral.com)
By comparing the transcriptional responses to both types of DNA damage, we can compare the similarities in the responses to damage as well as the differences induced by genotoxic damage. (biomedcentral.com)

Using a competition assay on agarose gels we found that the p53 consensus sequences in longer DNA fragments are better targets than the same sequences in shorter DNAs. (nih.gov)
Another 2011 study found that the p53 homozygous (Pro/Pro) genotype was associated with a significantly increased risk for renal cell carcinoma. (wikipedia.org)

However, these modifications alone may not account in full for p53 stabilization, p53's stability and activity are negatively regulated by the oncoprotein MDM2, whose gene is activated by p53. (tau.ac.il)
Conceivably, p53 function may be modulated by modifications of MDM2 as well. (tau.ac.il)
These findings suggest that in response to DNA strand breaks, ATM may promote p53 activity and stability by mediating simultaneous phosphorylation of both partners of the p53-MDM2 autoregulatory feedback loop. (tau.ac.il)

The activity of the p53 tumor suppressor protein and the c-Jun protooncogene is regulated by posttranslational modifications, such as phosphorylation or ubiquitination. (cancer-pictures.org)
The activity of the p53 gene product is regulated by a plethora of posttranslational modifications. (rupress.org)

Microarray analyses of MCF-7 cells transfected with control or SMRT small interfering RNA revealed SMRT regulation of genes involved in DNA damage responses, and the levels of the DNA damage marker γH2AX as well as poly(ADP-ribose) polymerase cleavage were elevated in SMRT-depleted cells treated with doxorubicin. (nih.gov)

p53 is involved in mechanisms regulating many other cellular processes, including metabolism, autophagy, and cell migration and invasion, and these pathways might crucially contribute to its tumor suppressor function. (uni-konstanz.de)
Here, we review the role of ferroptosis in p53-mediated tumor suppression, with a focus on what cellular factors are critical for p53-dependent ferroptosis during tumor suppression and how p53 modulates both the canonical (GPX4-dependent) and the non-canonical (GPX4-independent) ferroptosis pathways. (nature.com)
Once activated, p53 coordinates multiple downstream pathways, thereby maintaining the homeostasis of the host cell or organism (if the stress is mild, transient, and repairable) or eliminating damaged cells (if the stress is acute, prolonged, and difficult to resist). (nature.com)

SMRT knockdown decreased the activity of two p53-dependent reporter genes as well as the expression of p53 target genes, such as CDKN1A (which encodes p21). (nih.gov)

However, the debate regarding which single function of p53 is absolutely critical for its tumor suppressor role is ongoing [ 7 ]. (nature.com)
In the study, the authors dissect a new mechanism driven by cutaneous beta human papillomavirus (HPV) type 38 in altering the function of p53. (who.int)

Since p53 could induce G2/M cell cycle arrest, the p53-present tumour cells were found to be more resistant to Andro-induced cell death, compared to the p53-deficient cells. (authorea.com)
Contradictory reports exist about the requirement for DNA-PK in vivo for p53 activation and cell cycle arrest in response to ionizing radiation. (uthscsa.edu)
While primary SCID (severe combined immunodeficiency) cells, that have defective DNA-PK, show normal p53 activation and cell cycle arrest, a transcriptionally inert form of p53 is induced in the SCID cell line SCGR11. (uthscsa.edu)
Several hallmarks of cellular senescence, such as cell cycle arrest, expression of cyclin-dependent kinase inhibitors, DNA damages, and senescence-associated secretory profile were evaluated. (aging-us.com)
SnCs exhibit irreversible growth arrest accompanied by increased expression of cyclin-dependent kinase inhibitors (CDKi) such as p16 INK4a , and p21 Cip1 , accumulation of DNA damages, and secretion of diverse bioactive molecules known as the senescence-associated secretory phenotype (SASP). (aging-us.com)

He adds that this could shed light on why cancers can develop despite apparently normal p53 genes. (newscientist.com)

Sometimes called the 'guardian of the genome,' p53 is a tumor suppressor gene that, when neutralized, plays a critical role in the development of many types of tumors. (mdanderson.org)
The initiation and development of tumor cell is accompanied by elevated stresses, such as oncogene activation, DNA damage, genome instability, and reprogrammed tumor metabolism. (nature.com)
It is a moment in which the cell automatically breaks DNA all along its genome. (scienceblog.com)
The genome is an organism's complete set of DNA. (jainworld.com)
Genomes vary widely in size: the smallest known genome for a free-living organism (a bacterium) contains about 600000 DNA base pairs, while human and mouse genomes have some 3 billion. (jainworld.com)
DNA in the human genome is arranged into 24 distinct chromosomes, physically separate molecules that range in length from about 50 million to 250 million base pairs. (jainworld.com)

This phosphorylation is independent of p53 and the DNA-dependent protein kinase. (tau.ac.il)
Phosphorylation at serine 15 of the human p53 tumor suppressor protein is induced by DNA damage and correlates with accumulation of p53 and its activation as a transcription factor. (uthscsa.edu)
In order to unambiguously define the role of the DNA-PK catalytic subunit (DNA-PKcs) in p53 activation, we examined p53 phosphorylation in mouse embryonic fibroblasts (MEFs) from DNA-PKcs-null mice. (uthscsa.edu)
We found a similar pattern of serine 18 phosphorylation and accumulation of p53 in response to irradiation in both control and DNA-PKcs- null MEFs. (uthscsa.edu)
Firstly, DNA damage stabilizes SCML2 through CHK1-mediated phosphorylation at Ser570. (lucmg.com)
18-20 p16 INK4a shares functional similarities with p53 in that it blocks progression through the cell cycle at G1/S by inhibiting CDK 4/6 mediated phosphorylation of Rb. (bmj.com)

p53 directly regulates JMJD2B gene expression by binding to a canonical p53-consensus motif in the JMJD2B promoter. (escholarship.org)
Collectively, these data highlight a biological role for SMRT in mediating DNA damage responses and suggest a model where p53 binding to the DAD limits HDAC3 interaction with this coregulator, thereby facilitating SMRT coactivation of p53-dependent gene expression. (nih.gov)

To achieve this, p53 mainly functions as a transcription factor (TF) targeting hundreds of genes, but it also has TF-independent roles in the nucleus and cytoplasm [ 6 ]. (nature.com)

In p53-positive cancer cells, SCML2 competes with p53 for USP7 binding and destabilizes p53, which prevents DNA damage-induced p53 overactivation and increases chemoresistance. (lucmg.com)

Because of these limited therapeutic targets, many cancers, including TNBCs, are typically treated with surgery and a combination of radiation and chemotherapy that induce various types of DNA damage. (sciencedaily.com)
This study used etoposide, to induce DNA damage-related senescence or chronic exposure to IL-1β to entail inflammation-related senescence in human OA chondrocytes. (aging-us.com)

The protein regulates cell growth and division by monitoring DNA damage. (medlineplus.gov)

On the other hand, etoposide treatment reliably induces DNA damage-related senescence in human articular chondrocytes evidenced by loss of proliferative capacity, DNA damage accumulation, and expression of some SASP components. (aging-us.com)

We also discuss the possibility of targeting p53-mediated ferroptotic responses for the treatment of human cancers and potentially, other diseases. (nature.com)

The chemical modifications of the p53 protein that we thought were essential for its normal function may just fine-tune the activity of the protein under physiological conditions in a living organism, but they are not essential," explains lead investigator professor Geoffrey M. Wahl. (news-medical.net)

We assessed the impact of p53 protein phosphorylations on p53 functions as an alternative inactivation mechanism. (muni.cz)
Inactivation of p53 by Human papillomavirus (HPV) 16/18 E6 plays a crucial role in cervical tumorigenesis. (molvis.org)
In this study, we further speculate that p53 inactivation may be linked with HPV infection in pterygium pathogenesis. (molvis.org)
To investigate the involvement of HPV 16/18 E6 in p53 inactivation in pterygium, the association between HPV 16 or HPV 18 infection, the HPV E6 oncoprotein, and p53 protein expression was analyzed in this study. (molvis.org)
HPV 16/18 E6 contributes to HPV-mediated pterygium pathogenesis as it is partly involved in p53 inactivation and is expressed in HPV DNA-positive pterygium. (molvis.org)
In view of the comparable biological and phenotypic features of p53 and p16 INK4a inactivation, we proposed that germline inactivation of the p16 INK4a gene could account for the predisposition to cancer development in a proportion of LFS families that harboured wild type p53 . (bmj.com)

However, according to an increasing number of studies, the p53-mediated canonical DNA damage response is dispensable for tumor suppression. (uni-konstanz.de)
In this review we summarize the canonical and non-canonical functions of p53 in an attempt to provide an overview of the potentially crucial aspects related to its tumor suppressor activity. (uni-konstanz.de)

In this cell type, p53 activates numerous microRNAs (like miR-302a, miR-302b, miR-302c, and miR-302d) that directly inhibit the p21 expression in hESCs. (wikipedia.org)
Furthermore, Andro caused ROS-mediated DNA damage, which was critical for cell death. (authorea.com)
As a result, either silencing or knocking-out p62 promoted DNA damage repair and consequently protected HCC cells from Andro- induced cell death. (authorea.com)
Transactivation of the cyclin-dependent-kinase inhibitor p21, a downstream target of p53, and the G 1 cell cycle checkpoint were also found to be normal in the DNA-PKcs -/- MEFs. (uthscsa.edu)
The new research indicates that these modifications are not necessary to activate p53 under conditions of stress or to prevent p53 from throwing a wrench into the cell cycle machinery, when nothing is wrong. (news-medical.net)
Unless promptly and properly repaired, these DNA breaks can let cell division spiral out of control, ultimately causing cancer. (news-medical.net)
Under normal conditions, the p53 protein is very unstable and found only at very low levels in the cell. (news-medical.net)
But when the cell senses that its DNA has been damaged, it slows down the degradation of p53, so that p53 protein levels can rise and initiate protective measures. (news-medical.net)
Using a clinically guided genetic screening approach, researchers identified a non-coding RNA that is overexpressed in triple-negative breast cancer cells and regulated by the tumor suppressor p53 and the activated cell surface protein, EGFR. (sciencedaily.com)
This lncRNA is overexpressed in triple-negative breast cancer cells and regulated by the tumor suppressor p53 and the activated cell surface protein, EGFR. (sciencedaily.com)
Inhibition of VCP either by genetic depletion or the pharmacologic inhibitor CB-5083 increased ubiquitination and degradation of p53-R273H, leading to cell death. (aacrjournals.org)
The altered protein cannot regulate cell proliferation effectively and allows DNA damage to accumulate in cells. (medlineplus.gov)
The nucleus of a cell contains a chemical DNA (deoxyribonucleic acid). (jainworld.com)
All the instructions needed to direct the activities of cell are contained within the DNA. (jainworld.com)
Involved in signal transduction, cell cycle control and DNA repair. (lu.se)

Most studies in the p53 field have focused on its roles in tumors. (nature.com)
3) p53 null mice develop tumors with 100% penetrance. (nature.com)
When responding to these stresses, p53 may incidentally but efficiently suppress tumors. (nature.com)
p53, mdm-2, p21, and mib-1 expression were assessed by immunohistochemical methods in primary tumors derived from 134 patients who took part in a randomized multicenter trial comparing docetaxel to sequential methotrexate and 5-fluorouracil (MF) in advanced breast cancer. (lu.se)
Interestingly, tumors with both negative mdm-2 and p21 expression, irrespective of p53 status, had a high response rate to docetaxel but no response to MF. (lu.se)
Loss of heterozygosity at the p53 locus was not seen in the primary tumors of these women, but appeared as a partial loss of the wildtype allele in subsequent recurrent lesions of two gene carriers. (lu.se)

Notably, SCML2 promotes chemoresistance through distinct mechanisms in p53-positive and p53-negative cancer cells. (lucmg.com)

Although the cells produced abundant p53, it didn't get transported to the nucleus where it does its work. (newscientist.com)

p53-mediated ferroptosis is required for its tumor suppression in mouse models. (nature.com)
What is the physiological ferroptosis inducer(s) for p53 during tumor suppression? (nature.com)

The other half of cancers harbour a wild-type p53 gene whose tumour suppressor functions are altered by different mechanisms, which are not yet completely understood. (who.int)

Until now, many scientists thought that specific modifications on the easily accessible tail end, or C-terminus, of the p53 protein are crucial for both, timely degradation or activation. (news-medical.net)

One of the most important functions of the tumor suppressor p53 protein is its sequence-specific binding to DNA. (nih.gov)
We have solved the crystal structures of three oncogenic mutants of the core domain of the human tumor suppressor p53. (rcsb.org)
The p53 tumor-suppressor protein, a key regulator of cellular responses to genotoxic stress, is stabilized and activated after DNA damage. (tau.ac.il)
The cellular cascade of molecular signals that instructs cells with fatally damaged DNA to self-destruct pivots on the p53 tumor suppressor gene. (news-medical.net)
Or, if the damage is too severe for the breaks to be repaired, critical backup protection, also governed by the p53 tumor suppressor protein, kicks in. (news-medical.net)
From an evolutionary point of view it is understandable to think that p53 came into existence without necessarily acting as a tumour suppressor and, therefore, must have had other functions which until now remained unknown. (scienceblog.com)
In a new article, scientists from the International Agency for Research on Cancer (IARC) and partners describe a novel virus-driven mechanism that converts p53 from a tumour suppressor protein into a pro-proliferative factor. (who.int)

Results PIAS1 and PIASx Stimulate Sumoylation of p53 and c-Jun sumoylation assay, where a 35S-labeled substrate, generated by translation, serves as a target for SUMO changes in the presence of recombinant E1 (the Aos1/Uba2 heterodimer), recombinant Ubc9, SUMO-1, and ATP. (cancer-pictures.org)

Since the p53 protein is able to trigger such drastic action as cellular suicide, the cells of the body must ensure that the p53 protein is only activated when damage is sensed and that the protein is quickly degraded when it is not needed. (news-medical.net)
Researchers have extensively studied factors known to damage DNA, such as UV light and tobacco smoke, along with the cellular mechanisms of DNA repair. (nih.gov)
Double strand (ds) DNA breaks are a form of DNA damage that can be generated from both genotoxic exposures and physiologic processes, can disrupt cellular functions and can be lethal if not repaired properly. (biomedcentral.com)
Ionizing radiation can cause DSBs, as well as other DNA lesions, and has been shown to disrupt many cellular functions. (biomedcentral.com)

This process is associated with posttranslational modifications of p53, some of which are mediated by the ATM protein kinase. (tau.ac.il)

A number of these genes are established p53 targets. (nih.gov)
instead, through its metabolic targets, p53 is able to modulate the ferroptosis response in the presence of ferroptosis inducers such as GPX4 inhibitors or high levels of ROS. (nature.com)

A new mouse model, created by scientists at the Salk Institute for Biological Studies , suggests that what researchers have learned about the regulation of p53 activity from in vitro studies may not be relevant to living, breathing organisms. (news-medical.net)
The protein product of the murine double minute gene 2 (mdm-2) plays a central role in the regulation of p53. (lu.se)

It has two main isoforms: TAp63 has an N-terminal TA homologous to that of p53, while ΔNp63 has a truncated but specific TA domain, the expression of which depends on selective promoters. (researchsquare.com)
The DNA-dependent protein kinase (DNA- PK) can phosphorylate serine 15 of human p53 and the homologous serine 18 of murine p53 in vitro. (uthscsa.edu)

Functionally, exogenous expression of JMJD2B enhanced subcutaneous tumor growth of colon cancer cells in a p53-dependent manner, and genetic inhibition of JMJD2B impaired tumor growth in vivo. (escholarship.org)

Our cells are vulnerable to DNA breaks caused by UV light, ionizing radiation, toxic chemicals or other environmental damages. (news-medical.net)

P53 is in charge of developing this process control mechanism. (scienceblog.com)

This p53-repressive activity may cause genomic instability in epithelial stem cells exposed to radiation. (researchsquare.com)
To elucidate the role of the p53-repressive effect of ΔNp63α in radiation response, we performed a p63-siRNA knockdown experiment using human mammary epithelial cells (HMECs) expressing ΔNp63α and then performed ectopic and entopic expression experiments using human induced pluripotent stem cells (hiPSCs). (researchsquare.com)
Cells were transfected in six-well dishes as explained above by using 200 ng of a firefly luciferase reporter gene plasmid (pRGC, provided by M. Oren) that harbors a p53 DNA binding site in its promoter. (cancer-pictures.org)
Until now, scientists had assumed, based on studies in cultured cells, that p53 had to be modified by attaching chemical groups to specific sites on the protein to function normally in the body. (news-medical.net)
This may have an important impact in understanding the biology of wild-type p53 in cancer-transformed cells. (who.int)
p53 is a key protein that is altered in all cancer cells. (who.int)
We hypothesized that DA WT cells might undergo changes, such as acquiring a persistent tolerance to DNA damage and copy number aberrations (CNAs), which could eventually lead to their resistance to chemotherapy treatment. (lu.se)
In conclusion, we suggest that chemoresistance of DA WTs may be partly explained by a high proliferative capability of anaplastic cells, which also have a high burden of double-stranded DNA breaks and CNAs, and that there is a gradual emergence of anaplasia in WT. (lu.se)

HBV demonstrates the ability to integrate and bind to p53 protein in the host DNA and propagate hepatocyte vulnerability through carcinogenic aflatoxin B1 (AFB1) damage. (bvsalud.org)

The gene p53 suppresses cancer and inflammation in the body, and NIEHS investigators speculate that changes in p53 lead to changes in inflammation and the ability to repair DNA damage. (nih.gov)

All regions were scored for anaplastic features and immunohistochemistry was used to quantify p53 expression, proliferation index (Ki67), and DNA double-strand breaks (γH2AX). (lu.se)
Proliferation index and the frequency of DNA double-strand breaks (γH2AX dot expression) increased with higher anaplasia scores. (lu.se)

Mutations15

Apoptosis17

TP536

Protein p533

Mutation8

Response to DNA damage4

Pathway12

Role of p532

Activation of p532

Mutant7

Proteins11

Transcriptional8

Found that the p532

Mdm23

Activity of the p532

Genes Involved1

Pathways3

Expression of p531

Function of p532

Arrest5

Normal p531

Genome6

Phosphorylation6

Gene expression2

Transcription factor1

Damage induced1

Induce2

Regulates1

Accumulation1

Human cancers1

Organism1

Inactivation6

Canonical2

Cell15

Tumors6

Distinct1

Nucleus1

Tumor suppression2

Cancers1

Degradation1

Suppressor7

Assay1

Cellular4

Posttranslational modifications1

Targets2

Regulation2

Homologous2

Genetic1

Ionizing radiation1

Mechanism1

Cells8

Bind1

Repair1

Proliferation2