Mutant B-RAF signaling and cyclin D1 regulate Cks1/S-phase kinase-associated protein 2-mediated degradation of p27Kip1 in human melanoma cells.

Mutant B-RAF signaling and cyclin D1 regulate Cks1/S-phase kinase-associated protein 2-mediated degradation of p27Kip1 in human melanoma cells. Research Abstract Details 

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Mutant B-RAF signaling and cyclin D1 regulate Cks1/S-phase kinase-associated protein 2-mediated degradation of p27Kip1 in human melanoma cells. Abstract Text:

K V Bhatt,R Hu,L S Spofford,A E Aplin,

Levels of cyclins and cyclin-dependent kinase (Cdk) inhibitors are tightly controlled during normal cell proliferation and are frequently dysregulated in cancerous cells. In melanoma, cyclin D1 is highly expressed and downregulation of the Cdk inhibitor, p27(Kip1), is associated with a poor prognosis. Mutant B-RAF is frequently expressed in melanoma and overrides growth factor and matrix adhesion control of cyclin D1 and p27(Kip1) levels in human melanocytes. Here, we demonstrate that p27(Kip1) expression is regulated by multiple mechanisms in melanoma cells. B-RAF regulates p27(Kip1) mRNA abundance independently of cyclin D1. Additionally, B-RAF and cyclin D1 control the levels of S-phase kinase-associated protein 2 (Skp2) that directs ubiquitin-mediated proteolysis of p27(Kip1). The cofactor for Skp2, Cdc kinase subunit 1 (Cks1) controls levels of Skp2 in melanoma cells and acts jointly with Skp2 to regulate p27(Kip1) levels. Importantly, expression of Cks1 is regulated by B-RAF and cyclin D1 at the mRNA level. Reduced Cks1 or Skp2 expression and enhanced p27(Kip1) levels inhibit melanoma cell growth. In summary, p27(Kip1) expression in melanoma is regulated by B-RAF at the mRNA level, and via B-RAF and cyclin D1 control of Cks1/Skp2-mediated proteolysis.

Mutant B-RAF signaling and cyclin D1 regulate Cks1/S-phase kinase-associated protein 2-mediated degradation of p27Kip1 in human melanoma cells. Publishing Authors By Initials

KV Bhatt,R Hu,LS Spofford,AE Aplin,

For similar proteins: carrier proteins: s-phase kinase-associated proteins research abstracts see: proteins: carrier proteins: s-phase kinase-associated proteins research

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Mutant B-RAF signaling and cyclin D1 regulate Cks1/S-phase kinase-associated protein 2-mediated degradation of p27Kip1 in human melanoma cells. Journal Published:

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

Journal: Oncogene

VOLUME: 26

Page Numbers: 1056-66

Journal Abbreviation: Oncogene

ISSN: 0950-9232

DAY: 21

MONTH: 08

YEAR: 2006

Mutant B-RAF signaling and cyclin D1 regulate Cks1/S-phase kinase-associated protein 2-mediated degradation of p27Kip1 in human melanoma cells. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8711562

Mutant B-RAF signaling and cyclin D1 regulate Cks1/S-phase kinase-associated protein 2-mediated degradation of p27Kip1 in human melanoma cells. Keywords Mesh Terms:

KEYWORDS: S-Phase Kinase-Associated Proteins

MESH TERMS: physiology

Chemical & Substance for Abstract: Mutant B-RAF signaling and cyclin D1 regulate Cks1/S-phase kinase-associated protein 2-mediated degradation of p27Kip1 in human melanoma cells. Information

Substance Name: Proto-Oncogene Proteins B-raf

Registry Number: EC 2.7.1.37

Grant and Affiliation Information for Mutant B-RAF signaling and cyclin D1 regulate Cks1/S-phase kinase-associated protein 2-mediated degradation of p27Kip1 in human melanoma cells.

AFFILIATION: Center for Cell Biology and Cancer Research, 47 New Scotland Avenue, Albany Medical College, Albany, NY 12208, USA.

Country: England

AGENCY: United States NIGMS

GRANT: GM067893

ACRONYM: GM

MEDLINETA: Oncogene

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