p53

Summary

Gene Symbol: p53
Description: p53
Alias: CG10873, CG31325, CG33336, D-p53, DMP53, Dm-P53, DmP53, Dmel\CG33336, Dmp53, Dp53, dmp53, dp53, prac, p53, CG33336-PA, CG33336-PB, CG33336-PC, CG33336-PE, Dmp53, drosophila p53, p53-PA, p53-PB, p53-PC, p53-PE, p53-like regulator of apoptosis and cell cycle, protein 53
Species: fruit fly
Products:     p53

Top Publications

  1. Suissa Y, Ziv O, Dinur T, Arama E, Gerlitz O. The NAB-Brk signal bifurcates at JNK to independently induce apoptosis and compensatory proliferation. J Biol Chem. 2011;286:15556-64 pubmed publisher
    ..In particular, it was suggested that the initiator caspase Dronc mediates compensatory proliferation (CP) through Dp53 in wing discs. However, the exact mechanism that governs this CP remained poorly understood...
  2. Zhang Y, Lin N, Carroll P, Chan G, Guan B, Xiao H, et al. Epigenetic blocking of an enhancer region controls irradiation-induced proapoptotic gene expression in Drosophila embryos. Dev Cell. 2008;14:481-93 pubmed publisher
    ..Thus, direct epigenetic regulation of two proapoptotic genes controls cellular sensitivity to cytotoxic stimuli. ..
  3. Edwards A, Gladstone M, Yoon P, Raben D, Frederick B, Su T. Combinatorial effect of maytansinol and radiation in Drosophila and human cancer cells. Dis Model Mech. 2011;4:496-503 pubmed publisher
    ..We find that the effect of maytansinol is p53 dependent in Drosophila cells and human cancer cells, that maytansinol enhances the effect of radiation in both ..
  4. van Bergeijk P, Heimiller J, Uyetake L, Su T. Genome-wide expression analysis identifies a modulator of ionizing radiation-induced p53-independent apoptosis in Drosophila melanogaster. PLoS ONE. 2012;7:e36539 pubmed publisher
    Tumor suppressor p53 plays a key role in DNA damage responses in metazoa, yet more than half of human tumors show p53 deficiencies...
  5. Bodai L, Pardi N, Ujfaludi Z, Bereczki O, Komonyi O, Balint E, et al. Daxx-like protein of Drosophila interacts with Dmp53 and affects longevity and Ark mRNA level. J Biol Chem. 2007;282:36386-93 pubmed
    Daxx-like protein (DLP), the Drosophila homolog of Daxx, binds Drosophila melanogaster p53 (Dmp53) through its C-terminal region...
  6. Gowda P, Zhou F, Chadwell L, McEwen D. p53 binding prevents phosphatase-mediated inactivation of diphosphorylated c-Jun N-terminal kinase. J Biol Chem. 2012;287:17554-67 pubmed publisher
    ..the normally rapid JNK-dependent apoptotic response to genotoxic stress is significantly delayed in Dmp53 (Drosophila p53) mutants...
  7. de la Cova C, Senoo Matsuda N, Ziosi M, Wu D, Bellosta P, Quinzii C, et al. Supercompetitor status of Drosophila Myc cells requires p53 as a fitness sensor to reprogram metabolism and promote viability. Cell Metab. 2014;19:470-83 pubmed publisher
    ..that such confrontation enhances glycolytic flux in Myc cells and promotes their fitness and proliferation in a p53-dependent manner...
  8. Rong Y, Titen S, Xie H, Golic M, Bastiani M, Bandyopadhyay P, et al. Targeted mutagenesis by homologous recombination in D. melanogaster. Genes Dev. 2002;16:1568-81 pubmed
    ..developed method to produce mutant alleles of five endogenous Drosophila genes, including the homolog of the p53 tumor suppressor...
  9. Peng J, Karpen G. Heterochromatic genome stability requires regulators of histone H3 K9 methylation. PLoS Genet. 2009;5:e1000435 pubmed publisher
    ..Similar effects of lower magnitude were observed in animals that lack the RNA interference pathway component Dcr2. These results suggest that the H3K9 methylation and RNAi pathways ensure heterochromatin stability. ..

More Information

Publications68

  1. Owusu Ansah E, Yavari A, Mandal S, Banerjee U. Distinct mitochondrial retrograde signals control the G1-S cell cycle checkpoint. Nat Genet. 2008;40:356-61 pubmed publisher
    ..Thus, our results indicate that the mitochondrion can use AMP and ROS at sublethal concentrations as independent signaling molecules to modulate cell cycle progression. ..
  2. Colombani J, Polesello C, Josué F, Tapon N. Dmp53 activates the Hippo pathway to promote cell death in response to DNA damage. Curr Biol. 2006;16:1453-8 pubmed
    ..Here, we show that Hpo can be activated by Ionizing Radiations (IR) in a Dmp53 (Drosophila melanogaster p53)-dependent manner and that Hpo is required (though not absolutely) for the cell death ..
  3. Mendes C, Levet C, Chatelain G, Dourlen P, Fouillet A, Dichtel Danjoy M, et al. ER stress protects from retinal degeneration. EMBO J. 2009;28:1296-307 pubmed publisher
    ..We propose that an immediate consequence of the UPR not only limits the accumulation of misfolded proteins but also protects tissues from harmful exogenous stresses. ..
  4. Ahamed M, Posgai R, Gorey T, Nielsen M, Hussain S, Rowe J. Silver nanoparticles induced heat shock protein 70, oxidative stress and apoptosis in Drosophila melanogaster. Toxicol Appl Pharmacol. 2010;242:263-9 pubmed publisher
    ..Furthermore, Ag NPs up-regulated the cell cycle checkpoint p53 and cell signaling protein p38 that are involved in the DNA damage repair pathway...
  5. Brodsky M, Nordstrom W, Tsang G, Kwan E, Rubin G, Abrams J. Drosophila p53 binds a damage response element at the reaper locus. Cell. 2000;101:103-13 pubmed
    ..We describe a Drosophila p53 homolog and demonstrate that it can activate transcription from a promoter containing binding sites for human ..
  6. Allton K, Jain A, Herz H, Tsai W, Jung S, Qin J, et al. Trim24 targets endogenous p53 for degradation. Proc Natl Acad Sci U S A. 2009;106:11612-6 pubmed publisher
    Numerous studies focus on the tumor suppressor p53 as a protector of genomic stability, mediator of cell cycle arrest and apoptosis, and target of mutation in 50% of all human cancers...
  7. Beaucher M, Zheng X, Amariei F, Rong Y. Multiple pathways suppress telomere addition to DNA breaks in the Drosophila germline. Genetics. 2012;191:407-17 pubmed publisher
    ..Our study identifies several pathways that suppress telomere addition at DSBs, paving the way for future mechanistic studies. ..
  8. Ollmann M, Young L, Di Como C, Karim F, Belvin M, Robertson S, et al. Drosophila p53 is a structural and functional homolog of the tumor suppressor p53. Cell. 2000;101:91-101 pubmed
    ..We have identified a Drosophila homolog of p53 ("Dmp53")...
  9. Wichmann A, Uyetake L, Su T. E2F1 and E2F2 have opposite effects on radiation-induced p53-independent apoptosis in Drosophila. Dev Biol. 2010;346:80-9 pubmed publisher
    The ability of ionizing radiation (IR) to induce apoptosis independent of p53 is crucial for successful therapy of cancers bearing p53 mutations...
  10. Chen S, Wei H, Lv W, Wang D, Sun F. E2 ligase dRad6 regulates DMP53 turnover in Drosophila. J Biol Chem. 2011;286:9020-30 pubmed publisher
    ..However, the pathway that regulates the turnover of the Drosophila melanogaster DMP53 is largely unknown...
  11. Bauer J, Poon P, Glatt Deeley H, Abrams J, Helfand S. Neuronal expression of p53 dominant-negative proteins in adult Drosophila melanogaster extends life span. Curr Biol. 2005;15:2063-8 pubmed
    Hyperactivation of p53 leads to a reduction in tumor formation and an unexpected shortening of life span in two different model systems ...
  12. Brandt T, Kaar J, Fersht A, Veprintsev D. Stability of p53 homologs. PLoS ONE. 2012;7:e47889 pubmed publisher
    ..Some are only marginally stable, as for example, the DNA-binding domains of p53 and its homologs, whose kinetic and thermodynamic stabilities are strongly correlated...
  13. Jin S, Martinek S, Joo W, Wortman J, Mirkovic N, Sali A, et al. Identification and characterization of a p53 homologue in Drosophila melanogaster. Proc Natl Acad Sci U S A. 2000;97:7301-6 pubmed
    ..Here we report the identification and characterization of a Drosophila p53 homologue gene, dp53...
  14. Mesquita D, Dekanty A, Milan M. A dp53-dependent mechanism involved in coordinating tissue growth in Drosophila. PLoS Biol. 2010;8:e1000566 pubmed publisher
    ..Strikingly, we underscore a central role of Drosophila p53 (dp53) and the apoptotic machinery in these processes...
  15. Moon N, Di Stefano L, Morris E, Patel R, White K, Dyson N. E2F and p53 induce apoptosis independently during Drosophila development but intersect in the context of DNA damage. PLoS Genet. 2008;4:e1000153 pubmed publisher
    ..induced by the deregulation of dE2F1, or by the overexpression of dE2F1, is unaffected by the elimination of dp53; conversely, dp53-induced phenotypes are unaffected by the elimination of dE2F activity...
  16. Wylie A, Lu W, D Brot A, Buszczak M, Abrams J. p53 activity is selectively licensed in the Drosophila stem cell compartment. elife. 2014;3:e01530 pubmed publisher
    ..Using a biosensor to visualize p53 action, we find that Drosophila p53 is selectively active in gonadal stem cells after exposure to stressors that destabilize the genome...
  17. Morris E, Michaud W, Ji J, Moon N, Rocco J, Dyson N. Functional identification of Api5 as a suppressor of E2F-dependent apoptosis in vivo. PLoS Genet. 2006;2:e196 pubmed
    ..Therefore, inhibition of Api5 function might offer a possible mechanism for antitumor exploitation. ..
  18. Jaklevic B, Su T. Relative contribution of DNA repair, cell cycle checkpoints, and cell death to survival after DNA damage in Drosophila larvae. Curr Biol. 2004;14:23-32 pubmed
    ..All undergo radiation-induced apoptosis. p53 mutants regulate the cell cycle but fail to undergo apoptosis...
  19. Sogame N, Kim M, Abrams J. Drosophila p53 preserves genomic stability by regulating cell death. Proc Natl Acad Sci U S A. 2003;100:4696-701 pubmed
    ..To study its functions in vivo we produced a targeted mutation at the Drosophila p53 (Dmp53) locus. We show that Dmp53 is required for damage-induced apoptosis but not for cell-cycle arrest...
  20. Kurzhals R, Titen S, Xie H, Golic K. Chk2 and p53 are haploinsufficient with dependent and independent functions to eliminate cells after telomere loss. PLoS Genet. 2011;7:e1002103 pubmed publisher
    ..Here we show that p53 and Chk2 limit the growth and differentiation of cells that lose a telomere...
  21. Wells B, Johnston L. Maintenance of imaginal disc plasticity and regenerative potential in Drosophila by p53. Dev Biol. 2012;361:263-76 pubmed publisher
    Following irradiation (IR), the DNA damage response (DDR) activates p53, which triggers death of cells in which repair cannot be completed. Lost tissue is then replaced and re-patterned through regeneration...
  22. Yamada Y, Davis K, Coffman C. Programmed cell death of primordial germ cells in Drosophila is regulated by p53 and the Outsiders monocarboxylate transporter. Development. 2008;135:207-16 pubmed
    ..This germ cell death is mediated by Drosophila p53 (p53). Mutations in p53 result in excess primordial germ cells that are ectopic to the gonads...
  23. Abdu U, Brodsky M, Schupbach T. Activation of a meiotic checkpoint during Drosophila oogenesis regulates the translation of Gurken through Chk2/Mnk. Curr Biol. 2002;12:1645-51 pubmed
    ..In addition, we found that p53 and mus304, the Drosophila ATR-IP homolog, are not required for the patterning defects caused by the meiotic DNA ..
  24. Peters M, DeLuca C, Hirao A, Stambolic V, Potter J, Zhou L, et al. Chk2 regulates irradiation-induced, p53-mediated apoptosis in Drosophila. Proc Natl Acad Sci U S A. 2002;99:11305-10 pubmed
    ..Overexpression of D. melanogaster p53 (Dmp53) in the eye induced apoptosis, resulting in a small eye phenotype...
  25. Wichmann A, Jaklevic B, Su T. Ionizing radiation induces caspase-dependent but Chk2- and p53-independent cell death in Drosophila melanogaster. Proc Natl Acad Sci U S A. 2006;103:9952-7 pubmed
    Ionizing radiation (IR) can induce apoptosis via p53, which is the most commonly mutated gene in human cancers. Loss of p53, however, can render cancer cells refractory to therapeutic effects of IR...
  26. Monk A, Abud H, Hime G. Dmp53 is sequestered to nuclear bodies in spermatogonia of Drosophila melanogaster. Cell Tissue Res. 2012;350:385-94 pubmed publisher
    ..The Drosophila family member, Dmp53, primarily functions to regulate apoptosis in developing and regenerating tissues but loss of function mutants are ..
  27. Peterson C, Carney G, Taylor B, White K. reaper is required for neuroblast apoptosis during Drosophila development. Development. 2002;129:1467-76 pubmed
    ..Although both the ecdysone hormone receptor complex and p53 directly regulate rpr transcription, rpr was found to play a limited role in inducing apoptosis in response to ..
  28. Ou H, Lohr F, Vogel V, Mäntele W, Dötsch V. Structural evolution of C-terminal domains in the p53 family. EMBO J. 2007;26:3463-73 pubmed
    ..The Dmp53 structure is characterized by an additional N-terminal beta-strand and a C-terminal helix...
  29. Wells B, Yoshida E, Johnston L. Compensatory proliferation in Drosophila imaginal discs requires Dronc-dependent p53 activity. Curr Biol. 2006;16:1606-15 pubmed
    ..Here we provide evidence that Drosophila p53 (dp53) has a previously unidentified role in coordinating the compensatory growth response to tissue damage...
  30. Kim H, Lee J, Lee G, Bhin J, Oh S, Kim K, et al. DNA damage-induced ROR? is crucial for p53 stabilization and increased apoptosis. Mol Cell. 2011;44:797-810 pubmed publisher
    A critical component of the DNA damage response is the p53 tumor suppressor, and aberrant p53 function leads to uncontrolled cell proliferation and malignancy...
  31. Kondo S, Senoo Matsuda N, Hiromi Y, Miura M. DRONC coordinates cell death and compensatory proliferation. Mol Cell Biol. 2006;26:7258-68 pubmed
    ..These results show that the apoptotic pathway bifurcates at DRONC and that DRONC coordinates the execution of cell death and compensatory proliferation. ..
  32. Jassim O, Fink J, Cagan R. Dmp53 protects the Drosophila retina during a developmentally regulated DNA damage response. EMBO J. 2003;22:5622-32 pubmed
    ..In contrast, we found that Reaper had no effect on UV sensitivity. Surprisingly, Dmp53 is required to protect cells from UV-mediated cell death, an effect attributed to its role in DNA repair...
  33. Steller H. Drosophila p53: meeting the Grim Reaper. Nat Cell Biol. 2000;2:E100-2 pubmed
    The recent discovery of a Drosophila orthologue of the p53 tumour suppressor promises new insights into the complex function, regulation and evolution of one of the most intensely studied human disease proteins.
  34. Mandal S, Freije W, Guptan P, Banerjee U. Metabolic control of G1-S transition: cyclin E degradation by p53-induced activation of the ubiquitin-proteasome system. J Cell Biol. 2010;188:473-9 pubmed publisher
    ..of the mitochondrial electron transport chain activates a G1-S checkpoint as a result of a control of cyclin E by p53. This regulation does not involve activation of the p27 homologue dacapo in flies...
  35. Bakhrat A, Pritchett T, Peretz G, McCall K, Abdu U. Drosophila Chk2 and p53 proteins induce stage-specific cell death independently during oogenesis. Apoptosis. 2010;15:1425-34 pubmed publisher
    In Drosophila, the checkpoint protein-2 kinase (DmChk2) and its downstream effector protein, Dmp53, are required for DNA damage-mediated cell cycle arrest, DNA repair and apoptosis...
  36. Bi X, Gong M, Srikanta D, Rong Y. Drosophila ATM and Mre11 are essential for the G2/M checkpoint induced by low-dose irradiation. Genetics. 2005;171:845-7 pubmed
  37. Bauer J, Chang C, Morris S, Hozier S, Andersen S, Waitzman J, et al. Expression of dominant-negative Dmp53 in the adult fly brain inhibits insulin signaling. Proc Natl Acad Sci U S A. 2007;104:13355-60 pubmed
    In Drosophila melanogaster, p53 (Dmp53) is an important mediator of longevity. Expression of dominant-negative (DN) forms of Dmp53 in adult neurons, but not in muscle or fat body cells, extends lifespan...
  38. Mandal S, Guptan P, Owusu Ansah E, Banerjee U. Mitochondrial regulation of cell cycle progression during development as revealed by the tenured mutation in Drosophila. Dev Cell. 2005;9:843-54 pubmed
    ..Analysis of this gene in vivo and in cell lines shows that a specific pathway involving AMPK and p53 is activated that causes elimination of Cyclin E, resulting in cell cycle arrest...
  39. Sekelsky J, Brodsky M, Burtis K. DNA repair in Drosophila: insights from the Drosophila genome sequence. J Cell Biol. 2000;150:F31-6 pubmed
  40. Jiang H, Patel P, Kohlmaier A, Grenley M, McEwen D, Edgar B. Cytokine/Jak/Stat signaling mediates regeneration and homeostasis in the Drosophila midgut. Cell. 2009;137:1343-55 pubmed publisher
    ..Hence, cytokine-mediated feedback enables stem cells to replace spent progeny as they are lost, thereby establishing gut homeostasis. ..
  41. Song Y, Mirey G, Betson M, Haber D, Settleman J. The Drosophila ATM ortholog, dATM, mediates the response to ionizing radiation and to spontaneous DNA damage during development. Curr Biol. 2004;14:1354-9 pubmed
    ..Developing larval discs exhibit substantially increased spontaneous chromosomal telomere fusions and p53-dependent apoptosis...
  42. Hong Y, Lee N, Lee M, Park M, Choi G, Suh Y, et al. dXNP/DATRX increases apoptosis via the JNK and dFOXO pathway in Drosophila neurons. Biochem Biophys Res Commun. 2009;384:160-6 pubmed publisher
    ..These results suggest that dXNP/DATRX is involved in caspase-dependent apoptosis in Drosophila neurons via regulation of the JNK and dFOXO pathway. ..
  43. Dichtel Danjoy M, Ma D, Dourlen P, Chatelain G, Napoletano F, Robin M, et al. Drosophila p53 isoforms differentially regulate apoptosis and apoptosis-induced proliferation. Cell Death Differ. 2013;20:108-16 pubmed publisher
    ..The Drosophila p53 gene structure is conserved and encodes at least two protein isoforms: a full-length isoform (Dp53) and an N-..
  44. Titen S, Golic K. Telomere loss provokes multiple pathways to apoptosis and produces genomic instability in Drosophila melanogaster. Genetics. 2008;180:1821-32 pubmed publisher
    ..The most prominent outcome of this event is cell death through Chk2 and Chk1 controlled p53-dependent apoptotic pathways...
  45. Ma X, Huang J, Yang L, Yang Y, Li W, Xue L. NOPO modulates Egr-induced JNK-independent cell death in Drosophila. Cell Res. 2012;22:425-31 pubmed publisher
    ..Our results indicate that the Ben-dUEV1a complex constitutes a molecular switch that bifurcates the Egr-induced cell death signaling into two pathways mediated by JNK and caspases respectively. ..
  46. Shlevkov E, Morata G. A dp53/JNK-dependant feedback amplification loop is essential for the apoptotic response to stress in Drosophila. Cell Death Differ. 2012;19:451-60 pubmed publisher
    ..In stress-induced apoptosis, the dp53 (Drosophila p53) gene and the Jun N-terminal kinase (JNK) pathway function upstream in the activation of the proapoptotic ..
  47. Mehrotra S, Maqbool S, Kolpakas A, Murnen K, Calvi B. Endocycling cells do not apoptose in response to DNA rereplication genotoxic stress. Genes Dev. 2008;22:3158-71 pubmed publisher
    ..In most cells, this rereplication triggers caspase activation and apoptotic cell death mediated by both p53-dependent and -independent pathways...
  48. Fan Y, Lee T, Xu D, Chen Z, Lamblin A, Steller H, et al. Dual roles of Drosophila p53 in cell death and cell differentiation. Cell Death Differ. 2010;17:912-21 pubmed publisher
    ..The Drosophila genome contains only one p53 homolog, Dp53. Previous work has established that Drosophila p53 (Dp53) induces apoptosis, but not cell-cycle arrest...
  49. Herzog G, Joerger A, Shmueli M, Fersht A, Gazit E, Segal D. Evaluating Drosophila p53 as a model system for studying cancer mutations. J Biol Chem. 2012;287:44330-7 pubmed publisher
    ..b>Drosophila p53 (Dmp53) has similar apoptotic functions as its human homolog and is therefore an attractive model system for ..
  50. Bourdon J, Fernandes K, Murray Zmijewski F, Liu G, Diot A, Xirodimas D, et al. p53 isoforms can regulate p53 transcriptional activity. Genes Dev. 2005;19:2122-37 pubmed
    The recently discovered p53-related genes, p73 and p63, express multiple splice variants and N-terminally truncated forms initiated from an alternative promoter in intron 3...
  51. McEwen D, Peifer M. Puckered, a Drosophila MAPK phosphatase, ensures cell viability by antagonizing JNK-induced apoptosis. Development. 2005;132:3935-46 pubmed
    ..Radiation upregulates both JNK activity and puc expression in a p53-dependent manner, and apoptosis induced by loss of Puc can be suppressed by p53 inactivation...
  52. Oikemus S, McGinnis N, Queiroz Machado J, Tukachinsky H, Takada S, Sunkel C, et al. Drosophila atm/telomere fusion is required for telomeric localization of HP1 and telomere position effect. Genes Dev. 2004;18:1850-61 pubmed
    ..Suppression of this apoptosis by p53 mutations suggests that loss of ATM activates apoptosis through a DNA damage-response mechanism...
  53. Lu W, Chapo J, Roig I, Abrams J. Meiotic recombination provokes functional activation of the p53 regulatory network. Science. 2010;328:1278-81 pubmed publisher
    The evolutionary appearance of p53 protein probably preceded its role in tumor suppression, suggesting that there may be unappreciated functions for this protein...
  54. Martín F, Pérez Garijo A, Morata G. Apoptosis in Drosophila: compensatory proliferation and undead cells. Int J Dev Biol. 2009;53:1341-7 pubmed publisher
    ..We describe their effects in epithelial architecture and growth in some detail, and discuss the possible relationship between undead cells and compensatory proliferation. ..
  55. Lee J, Lee E, Park J, Kim E, Kim J, Chung J. In vivo p53 function is indispensable for DNA damage-induced apoptotic signaling in Drosophila. FEBS Lett. 2003;550:5-10 pubmed
    ..Here we isolated flies lacking Dmp53, which encodes the single Drosophila orthologue of mammalian p53 family...
  56. McNamee L, Brodsky M. p53-independent apoptosis limits DNA damage-induced aneuploidy. Genetics. 2009;182:423-35 pubmed publisher
    ..telomeres can trigger apoptosis via signaling pathways that directly sense abnormal DNA structures and activate the p53 transcription factor...
  57. Fan Y, Bergmann A. Distinct mechanisms of apoptosis-induced compensatory proliferation in proliferating and differentiating tissues in the Drosophila eye. Dev Cell. 2008;14:399-410 pubmed publisher
    ..In summary, dependent on the developmental potential of the affected tissue, different caspases trigger distinct forms of compensatory proliferation in an apparent nonapoptotic function. ..
  58. Xie H, Golic K. Gene deletions by ends-in targeting in Drosophila melanogaster. Genetics. 2004;168:1477-89 pubmed
    ..Unlike ends-out targeting, this method does not leave exogenous sequence at the deleted locus. Three endogenous genes, Sir2, Sirt2, and p53 have been successfully deleted using this method.
  59. Luo X, Puig O, Hyun J, Bohmann D, Jasper H. Foxo and Fos regulate the decision between cell death and survival in response to UV irradiation. EMBO J. 2007;26:380-90 pubmed
    ..These data suggest that integrating stress and survival signals through Foxo drives the decision between cell death and repair of damaged cells in vivo. ..