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oai:repisalud.isciii.es:20.500.12105/260892025-12-18T12:56:01Zcom_20.500.12105_2327com_20.500.12105_2290col_20.500.12105_16991

00925njm 22002777a 4500 dc Cuadrado Garcia, Ana author Lafarga, Vanesa author Cheung, Peter C F author Dolado, Ignacio author Llanos, Susana author Cohen, Philip author Nebreda, Angel R author 2007-04-18 The p38 mitogen-activated protein kinase (MAPK) signaling pathway plays an important role in stress-induced cell-fate decisions by orchestrating responses that go from cell-cycle arrest to apoptosis. We have identified a new p38 MAPK-regulated protein that we named p18(Hamlet), which becomes stabilized and accumulates in response to certain genotoxic stresses such as UV or cisplatin treatment. Overexpression of p18(Hamlet) is sufficient to induce apoptosis, whereas its downregulation reduces the apoptotic response to these DNA damage-inducing agents. We show that p18(Hamlet) interacts with p53 and stimulates the transcription of several proapoptotic p53 target genes such as PUMA and NOXA. This correlates with enhanced p18(Hamlet)-induced recruitment of p53 to the promoters. In proliferating cells, low steady-state levels of p18(Hamlet) are probably maintained by a p53-dependent negative feedback loop. Therefore, p18(Hamlet) is a new cell-fate regulator that links the p38 MAPK and p53 pathways and contributes to the establishment of p53-regulated stress responses. EMBO J . 2007 Apr 18;26(8):2115-26 EMBO Journal 17380123 https://hdl.handle.net/20.500.12105/26089 DNA-DAMAGE P21(WAF1/CIP1) EXPRESSION DIFFERENTIAL ACTIVATION ATAXIA-TELANGIECTASIA UV-IRRADIATION S-PHASE PHOSPHORYLATION p53 cells STABILITY A new p38 MAP kinase-regulated transcriptional coactivator that stimulates p53-dependent apoptosis.