Letter abstract
Nature Cell Biology 10, 1083 - 1089 (2008)
Published online: 10 August 2008 | doi:10.1038/ncb1768
The adaptor protein of the anaphase promoting complex Cdh1 is essential in maintaining replicative lifespan and in learning and memory
Min Li1, Yong-Hyun Shin1, Lingfei Hou3, Xingxu Huang1, Zhubo Wei1, Eric Klann3 & Pumin Zhang1,2
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.
- Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA.
- Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
- Center for Neural Science, New York University, New York, NY 10003, USA.
Correspondence to: Pumin Zhang1,2 e-mail: pzhang@bcm.tmc.edu
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
RESEARCH
Genomic stability and tumour suppression by the APC/C cofactor Cdh1Nature Cell Biology Article (01 Jul 2008)
Mitotic regulation of the human anaphase-promoting complex by phosphorylationThe EMBO Journal Article (15 Dec 2003)
Mitotic regulation of the human anaphase-promoting complex by phosphorylationThe EMBO Journal Article (15 Dec 2003)
Plk4 haploinsufficiency causes mitotic infidelity and carcinogenesisNature Genetics Letter (01 Aug 2005)
See all 9 matches for Research
