CKS1B, overexpressed in aggressive disease, regulates multiple myeloma growth and survival through SKP2- and p27Kip1-dependent and -independent mechanisms.

CKS1B, overexpressed in aggressive disease, regulates multiple myeloma growth and survival through SKP2- and p27Kip1-dependent and -independent mechanisms. Research Abstract Details 

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CKS1B, overexpressed in aggressive disease, regulates multiple myeloma growth and survival through SKP2- and p27Kip1-dependent and -independent mechanisms. Abstract Text:

Fenghuang Zhan,Simona Colla,Xiaosong Wu,Bangzheng Chen,James P Stewart,W Michael Kuehl,Bart Barlogie,John D Shaughnessy,

Overexpression of CKS1B, a gene mapping within a minimally amplified region between 153 to 154 Mb of chromosome 1q21, is linked to a poor prognosis in multiple myeloma (MM). CKS1B binds to and activates cyclin-dependent kinases and also interacts with SKP2 to promote the ubiquitination and proteasomal degradation of p27(Kip1). Overexpression of CKS1B or SKP2 contributes to increased p27(Kip1) turnover, cell proliferation, and a poor prognosis in many tumor types. Using 4 MM cell lines harboring MAF-, FGFR3/MMSET-, or CCND1-activating translocations, we show that lentiviral delivery of shRNA directed against CKS1B resulted in ablation of CKS1B mRNA and protein with concomitant stabilization of p27(Kip1), cell cycle arrest, and apoptosis. Although shRNA-mediated knockdown of SKP2 and forced expression of a nondegradable form of p27(Kip1) (p27(T187A)) led to cell cycle arrest, apoptosis was modest. Of importance, while knockdown of SKP2 or overexpression of p27(T187A) induced cell cycle arrest in KMS28PE, an MM cell line with biallelic deletion of CDKN1B/p27(Kip1), CKS1B ablation induced strong apoptosis. These data suggest that CKS1B influences myeloma cell growth and survival through SKP2- and p27(Kip1)-dependent and -independent mechanisms and that therapeutic strategies aimed at abolishing CKS1B function may hold promise for the treatment of high-risk disease for which effective therapies are currently lacking.

CKS1B, overexpressed in aggressive disease, regulates multiple myeloma growth and survival through SKP2- and p27Kip1-dependent and -independent mechanisms. Publishing Authors By Initials

F Zhan,S Colla,X Wu,B Chen,JP Stewart,WM Kuehl,B Barlogie,JD Shaughnessy,

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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CKS1B, overexpressed in aggressive disease, regulates multiple myeloma growth and survival through SKP2- and p27Kip1-dependent and -independent mechanisms. Journal Published:

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

Journal: Blood

VOLUME: 109

Page Numbers: 4995-5001

Journal Abbreviation: Blood

ISSN: 0006-4971

DAY: 15

MONTH: 02

YEAR: 2007

CKS1B, overexpressed in aggressive disease, regulates multiple myeloma growth and survival through SKP2- and p27Kip1-dependent and -independent mechanisms. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7603509

CKS1B, overexpressed in aggressive disease, regulates multiple myeloma growth and survival through SKP2- and p27Kip1-dependent and -independent mechanisms. Keywords Mesh Terms:

KEYWORDS: S-Phase Kinase-Associated Proteins

MESH TERMS: biosynthesis

Chemical & Substance for Abstract: CKS1B, overexpressed in aggressive disease, regulates multiple myeloma growth and survival through SKP2- and p27Kip1-dependent and -independent mechanisms. Information

Substance Name: Caspases

Registry Number: EC 3.4.22.-

Grant and Affiliation Information for CKS1B, overexpressed in aggressive disease, regulates multiple myeloma growth and survival through SKP2- and p27Kip1-dependent and -independent mechanisms.

AFFILIATION: Donna D and Donald M. Lambert Laboratory of Myeloma Genetics at the Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Little Rock, AR 72205, USA. zhanfenghuang@uams.edu

Country: United States

AGENCY: United States NCI

GRANT: CA 97513

ACRONYM: CA

MEDLINETA: Blood

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