ArticleThe Journal of biological chemistry2010
Gain of cellular adaptation due to prolonged p53 impairment leads to functional switchover from p53 to p73 during DNA damage in acute myeloid leukemia cells.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 38 citations in OpenAlex.
- Phase 1 dose escalation study of the MDM2 inhibitor milademetan as monotherapy and in combination with azacitidine in patients with myeloid malignancies.Cancer medicine · 2024Article
- Review
- The p53 family member p73 in the regulation of cell stress response.Biology direct · 2021Review
- Polygonatum sibiricum polysaccharide potentially attenuates diabetic retinal injury in a diabetic rat model.Journal of diabetes investigation · 2019Article
- MiR-1180-5p regulates apoptosis of Wilms' tumor by targetingOncoTargets and therapy · 2018Article
- Juglanin inhibits lung cancer by regulation of apoptosis, ROS and autophagy induction.Oncotarget · 2017Article
- Crocetin exploits p53-induced death domain (PIDD) and FAS-associated death domain (FADD) proteins to induce apoptosis in colorectal cancer.Scientific reports · 2016Article
- Article
- The Modulation of Apoptotic Pathways by Gammaherpesviruses.Frontiers in microbiology · 2016Review
- MEK inhibition prevents tumour-shed transforming growth factor-β-induced T-regulatory cell augmentation in tumour milieu.Immunology · 2015Article
- Curcumin and tumor immune-editing: resurrecting the immune system.Cell division · 2015Review
- Nuclear matrix protein SMAR1 represses c-Fos-mediated HPV18 E6 transcription through alteration of chromatin histone deacetylation.The Journal of biological chemistry · 2014Article
- ROS-PIASγ cross talk channelizes ATM signaling from resistance to apoptosis during chemosensitization of resistant tumors.Cell death & disease · 2014Article
- Calcarea carbonica induces apoptosis in cancer cells in p53-dependent manner via an immuno-modulatory circuit.BMC complementary and alternative medicine · 2013Article
- N-(phosphonacetyl)-L-aspartate induces TAp73-dependent apoptosis by modulating multiple Bcl-2 proteins: potential for cancer therapy.Oncogene · 2013Article
- Restoration of tumor suppressor p53 by differentially regulating pro- and anti-p53 networks in HPV-18-infected cervical cancer cells.Oncogene · 2012Article
- Cell cycle control in acute myeloid leukemia.American journal of cancer research · 2012Article
- Tetraarsenic Hexoxide Induces Beclin-1-Induced Autophagic Cell Death as well as Caspase-Dependent Apoptosis in U937 Human Leukemic Cells.Evidence-based complementary and alternative medicine : eCAM · 2012Article
- Curcumin enhances the efficacy of chemotherapy by tailoring p65NFκB-p300 cross-talk in favor of p53-p300 in breast cancer.The Journal of biological chemistry · 2011Article
- p73 as a pharmaceutical target for cancer therapy.Current pharmaceutical design · 2011Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor suppressor p53 plays the central role in regulating apoptosis in response to genotoxic stress. From an evolutionary perspective, the activity of p53 has to be backed up by other protein(s) in case of any functional impairment of this protein, to trigger DNA damage-induced apoptosis in cancer cells. We adopted multiple experimental approaches to demonstrate that in p53-impaired cancer cells, DNA damage caused accumulation of p53 paralogue p73 via Chk-1 that strongly impacted Bax expression and p53-independent apoptosis. On the contrary, when p53 function was restored by ectopic expression, Chk-2 induced p53 accumulation that in turn overshadowed p73 activity, suggesting an antagonistic interaction between p53 family members. To understand such interaction better, p53-expressing cells were impaired differentially for p53 activity. In wild-type p53-expressing cancer cells that were silenced for p53 for several generations, p73 was activated, whereas no such trend was observed when p53 was transiently silenced. Prolonged p53 interference, even in functional p53 settings, therefore, leads to the "gain of cellular adaptation" in a way that alters the cellular microenvironment in favor of p73 activation by altering p73-regulatory proteins, e.g. Chk1 activation and dominant negative p73 down-regulation. These findings not only unveil a hitherto unexplained mechanism underlying the functional switchover from p53 to p73, but also validate p73 as a promising and potential target for cancer therapy in the absence of functional p53.
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