The anaphase-promoting complex coordinates initiation of lens differentiation.

The anaphase-promoting complex coordinates initiation of lens differentiation. Research Abstract Details 

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The anaphase-promoting complex coordinates initiation of lens differentiation. Abstract Text:

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

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)-beta-signaling pathway. We have identified that Cdh1/APC, a critical ubiquitin protein ligase, plays an important role in regulating lens differentiation by facilitating TGF-beta-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-beta-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-beta-signaling-induced destruction of SnoN.

The anaphase-promoting complex coordinates initiation of lens differentiation. Publishing Authors By Initials

G Wu,S Glickstein,W Liu,T Fujita,W Li,Q Yang,R Duvoisin,Y Wan,

For similar enzymes and coenzymes: enzymes: ligases: ubiquitin-protein ligase complexes: ubiquitin-protein ligases research abstracts see: enzymes and coenzymes: enzymes: ligases: ubiquitin-protein ligase complexes: ubiquitin-protein ligases research

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The anaphase-promoting complex coordinates initiation of lens differentiation. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Molecular biology of the cell

VOLUME: 18

Page Numbers: 1018-29

Journal Abbreviation: Mol. Biol. Cell

ISSN: 1059-1524

DAY: 10

MONTH: 01

YEAR: 2007

The anaphase-promoting complex coordinates initiation of lens differentiation. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9201390

The anaphase-promoting complex coordinates initiation of lens differentiation. Keywords Mesh Terms:

KEYWORDS: Ubiquitin-Protein Ligases

MESH TERMS: metabolism

Chemical & Substance for Abstract: The anaphase-promoting complex coordinates initiation of lens differentiation. Information

Substance Name: anaphase-promoting complex

Registry Number: EC 6.3.2.19

Grant and Affiliation Information for The anaphase-promoting complex coordinates initiation of lens differentiation.

AFFILIATION: University of Pittsburgh Cancer Institute, Pittsburgh, PA 15312, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM070681

ACRONYM: GM

MEDLINETA: Mol Biol Cell

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