Regulation of p53 by Mdm2 E3 Ligase Function Is Dispensable in Embryogenesis and Development, but Essential in Response to DNA Damage
In: Cancer Cell, Jg. 26 (2014-08-01), S. 235-247
Online
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Zugriff:
Summary Mdm2 E3 ubiquitin ligase-mediated p53 degradation is generally accepted as the major mechanism for p53 regulation; nevertheless, the in vivo significance of this function has not been unequivocally established. Here, we have generated an Mdm2 Y487A knockin mouse; Mdm2 Y487A mutation inactivates Mdm2 E3 ligase function without affecting its ability to bind its homolog MdmX. Unexpectedly, Mdm2 Y487A/Y487A mice were viable and developed normally into adulthood. While disruption of Mdm2 E3 ligase function resulted in p53 accumulation, p53 transcriptional activity remained low; however, exposure to sublethal stress resulted in hyperactive p53 and p53-dependent mortality in Mdm2 Y487A/Y487A mice. These findings reveal a potentially dispensable nature for Mdm2 E3 ligase function in p53 regulation, providing insight that may affect how this pathway is targeted therapeutically.
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Regulation of p53 by Mdm2 E3 Ligase Function Is Dispensable in Embryogenesis and Development, but Essential in Response to DNA Damage
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Autor/in / Beteiligte Person: | Tollini, Laura A. ; Jin, Aiwen ; Park, Jikyoung ; Zhang, Yanping |
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Zeitschrift: | Cancer Cell, Jg. 26 (2014-08-01), S. 235-247 |
Veröffentlichung: | Elsevier BV, 2014 |
Medientyp: | unknown |
ISSN: | 1535-6108 (print) |
DOI: | 10.1016/j.ccr.2014.06.006 |
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