The adaptor protein of the anaphase promoting complex Cdh1 is essential in maintaining replicative lifespan and in learning and memory

Min Li, Yong Hyun Shin, Lingfei Hou, Xingxu Huang, Zhubo Wei, Eric Klann, Pumin Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

The anaphase promoting complex (APC) or cyclosome is a multi-subunit E3 ubiquitin ligase. Cdc20 (fizzy (fzy)) or p55CDC, and Cdh1 (Hct1, srw1 or fizzy-related 1 (fzr1)) encode two adaptor proteins that bring substrates to the APC. Both APC-Cdc20 and APC-Cdh1 have been implicated in the control of mitosis through mediating ubiquitination of mitotic regulators, such as cyclin B1 and securin. However, the importance of Cdh1 function in vivo and whether its function is redundant with that of Cdc20 are unclear. Here we have analysed mice lacking Cdh1. We show that Cdh1 is essential for placental development and that its deficiency causes early lethality. Cdh1-deficient mouse embryonic fibroblasts (MEFs) entered replicative senescence prematurely because of stabilization of Ets2 and subsequent activation of p16Ink4a expression. These results have uncovered an unexpected role of the APC in maintaining replicative lifespan of MEFs. Further, Cdh1 heterozygous mice show defects in late-phase long-term potentiation (L-LTP) in the hippocampus and are deficient in contextual fear-conditioning, suggesting that Cdh1 has a role in learning and memory.

Original languageEnglish (US)
Pages (from-to)1083-1089
Number of pages7
JournalNature Cell Biology
Volume10
Issue number9
DOIs
StatePublished - 2008

ASJC Scopus subject areas

  • Cell Biology

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