Skp2-mediated p27(Kip1) degradation during S/G2 phase progression of adipocyte hyperplasia.

Skp2-mediated p27(Kip1) degradation during S/G2 phase progression of adipocyte hyperplasia. Research Abstract Details 

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Skp2-mediated p27(Kip1) degradation during S/G2 phase progression of adipocyte hyperplasia. Abstract Text:

Corinth A Auld,Karishma M Fernandes,Ron F Morrison,

p27(Kip1), an important regulator of Cdk2 activity and G1/S transition, is tightly regulated in a cell-type and condition-specific manner to integrate mitogenic and differentiation signals governing cell cycle progression. We show that p27 protein levels progressively declined from mid-G1 through late-G2 phase as density-arrested 3T3-L1 preadipocytes synchronously reentered the cell cycle during early stages of adipocyte differentiation. This dramatic fall in p27 protein accumulation was due, at least in part, to a decrease in protein stability. Specific inhibitors of the 26S proteasome were shown to completely block the decrease in p27 protein levels throughout G1, increase the abundance of ubiquitylated p27 protein, and inhibit G1/S transition resulting in G1 arrest. It is further demonstrated that p27 was phosphorylated on threonine 187 during S phase progression by Cdk2 and that phosphorylated p27 was polyubiquitylated and degraded. Furthermore, we demonstrate that Skp2 and Cks1 dramatically increased during S/G2 phase progression concomitantly with the maximal fall in p27 protein. Complete knockdown of Skp2 with RNA interference partially prevented p27 degradation equivalent to that observed with Cdk2 blockade suggesting that the SCF(Skp2) E3 ligase and other proteasome-dependent mechanisms contribute to p27 degradation during preadipocyte replication. Interestingly, Skp2-mediated p27 degradation was not essential for G1/S or S/G2 transition as preadipocytes shifted from quiescence to proliferation during adipocyte hyperplasia. Finally, evidence is presented suggesting that elevated p27 protein in the absence of Skp2 was neutralized by sequestration of p27 protein into Cyclin D1/Cdk4 complexes.

Skp2-mediated p27(Kip1) degradation during S/G2 phase progression of adipocyte hyperplasia. Publishing Authors By Initials

CA Auld,KM Fernandes,RF Morrison,

For similar proteins: ubiquitins: ubiquitin research abstracts see: proteins: ubiquitins: ubiquitin research

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Skp2-mediated p27(Kip1) degradation during S/G2 phase progression of adipocyte hyperplasia. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of cellular physiology

VOLUME: 211

Page Numbers: 101-11

Journal Abbreviation: J. Cell. Physiol.

ISSN: 0021-9541

DAY: 3

MONTH: Apr

YEAR: 2007

Skp2-mediated p27(Kip1) degradation during S/G2 phase progression of adipocyte hyperplasia. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 50222

Skp2-mediated p27(Kip1) degradation during S/G2 phase progression of adipocyte hyperplasia. Keywords Mesh Terms:

KEYWORDS: Ubiquitin

MESH TERMS: metabolism

Chemical & Substance for Abstract: Skp2-mediated p27(Kip1) degradation during S/G2 phase progression of adipocyte hyperplasia. Information

Substance Name: Proteasome Endopeptidase Complex

Registry Number: EC 3.4.25.1

Grant and Affiliation Information for Skp2-mediated p27(Kip1) degradation during S/G2 phase progression of adipocyte hyperplasia.

AFFILIATION: Department of Nutrition, The University of North Carolina at Greensboro, Greensboro, North Carolina 27402, USA.

Country: United States

AGENCY: United States NIDDK

GRANT: 1R21DK072067-01

ACRONYM: DK

MEDLINETA: J Cell Physiol

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