The anaphase-promoting complex coordinates initiation of lens differentiation

George Wu, Sara Glickstein, Weijun Liu, Takeo Fujita, Wenqi Li, Qi Yang, Robert Duvoisin, Yong Wan

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Lens development requires the precise coordination of cell division and differentiation. The mechanisms by which the differentiation program is initiated after cell cycle arrest remains not well understood. Cyclin-dependent kinase inhibitors (CKIs), such as p15 and p21, have been suggested to be critical components that inhibit G1 progression and therefore, their activation is necessary for quiescence and important for the onset of differentiation. Regulation of p15 and p21 is principally governed by transforming growth factor (TGF)-β-signaling pathway. We have identified that Cdh1/APC, a critical ubiquitin protein ligase, plays an important role in regulating lens differentiation by facilitating TGF-β-induced degradation of SnoN, a transcriptional corepressor that needs to be removed for transcriptional activation of p15 and p21. The depletion of Cdh1 by RNA interference attenuates the TGF-β-mediated induction of p15 and p21 and significantly blocks lens differentiation. Expression of nondegradable SnoN also noticeably attenuates lens induction. Furthermore, we have shown that Cdh1 and SnoN form a complex at the onset of lens differentiation. In vivo histological analysis confirms our biochemical and genetic results. Thus, Cdh1/APC is crucial to the coordination of cell cycle progression and the initiation of lens differentiation through mediating TGF-β-signaling-induced destruction of SnoN.

Original languageEnglish (US)
Pages (from-to)1018-1029
Number of pages12
JournalMolecular biology of the cell
Volume18
Issue number3
DOIs
StatePublished - Mar 2007

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'The anaphase-promoting complex coordinates initiation of lens differentiation'. Together they form a unique fingerprint.

  • Cite this