Community Research and Development Information Service - CORDIS

Effect of p73 on sensitivity to apoptosis

We have clarified the mechanisms through which p73 induces cell death. These mechanisms include regulation of Bax and PUMA as well as the control of the CD95 pathway. Moreover we have described the different roles of the TA (pro-apoptotic) and DN (anti-apoptotic) isoforms.

Finally we have identified a number of p73 interacting molecules that regulate its activity, this molecules include Itch, PIAS-1, Bub-1 and FLASH. Itch is an E3 ubiquitin ligase that specifically binds p73 but not p53 targeting it for degradation. Itch is down regulated in response to DNA damage allowing p73 levels to increase.

PIAS-1 is a SUMO E3 ligase that binds and sumoylates p73 decreasing its trascriptional activity in a cell cycle dependent manner. The interaction between Bub-1 and TAp73 explains the poliploidy observed in TAp73 over-expressing tumours. Finally we have shown that FLASH is an essential component of CBs that interacts with p73 and regulates histone transcription and cell cycle progression.

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UNIVERSITA DI ROMA TOR VERGATA
Dipartimento di Medicina Sperimentale, Via Montpellier 1
00133 ROMA
Italy
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