Atypical Protein Kinase C Regulates Dual Pathways for Degradation of the Oncogenic Coactivator SRC-3/AIB1.

Atypical Protein Kinase C Regulates Dual Pathways for Degradation of the Oncogenic Coactivator SRC-3/AIB1. Research Abstract Details 

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Atypical Protein Kinase C Regulates Dual Pathways for Degradation of the Oncogenic Coactivator SRC-3/AIB1. Abstract Text:

Ping Yi,Qin Feng,Larbi Amazit,David M Lonard,Sophia Y Tsai,Ming-Jer Tsai,Bert W O'Malley,

SRC-3/AIB1 is a steroid receptor coactivator with potent growth-promoting activity, and its overexpression is sufficient to induce tumorigenesis. Previous studies indicate that the cellular level of SRC-3 is tightly regulated by both ubiquitin-dependent and ubiquitin-independent proteasomal degradation pathways. Atypical protein kinase C (aPKC) is frequently overexpressed in cancers. In the present study, we show that aPKC phosphorylates and specifically stabilizes SRC-3 in a selective ER-dependent manner. We further demonstrate that an acidic residue-rich region in SRC-3 is an important determinant for aPKC-mediated phosphorylation and stabilization. The mechanism of the aPKC-mediated stabilization appears due to a decreased interaction between SRC-3 and the C8 subunit of the 20S core proteasome, thus preventing SRC-3 degradation. Our results demonstrate a potent signaling mechanism for regulating SRC-3 levels in cells by coordinate enzymatic inhibition of both ubiquitin-dependent and ubiquitin-independent proteolytic pathways.

Atypical Protein Kinase C Regulates Dual Pathways for Degradation of the Oncogenic Coactivator SRC-3/AIB1. Publishing Authors By Initials

P Yi,Q Feng,L Amazit,DM Lonard,SY Tsai,MJ Tsai,BW O'Malley,

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Atypical Protein Kinase C Regulates Dual Pathways for Degradation of the Oncogenic Coactivator SRC-3/AIB1. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Molecular cell

VOLUME: 29

Page Numbers: 465-76

Journal Abbreviation: Mol. Cell

ISSN: 1097-2765

DAY: 29

MONTH: Feb

YEAR: 2008

Atypical Protein Kinase C Regulates Dual Pathways for Degradation of the Oncogenic Coactivator SRC-3/AIB1. Information

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LANGUAGE: eng

NlmUniqueID: 9802571

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Grant and Affiliation Information for Atypical Protein Kinase C Regulates Dual Pathways for Degradation of the Oncogenic Coactivator SRC-3/AIB1.

AFFILIATION: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.

Country: United States

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MEDLINETA: Mol Cell

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