EMAIL THIS PAGE TO A FRIEND

PloS one

A critical role of CDKN3 in Bcr-Abl-mediated tumorigenesis.


PMID 25360622

Abstract

CDKN3 (cyclin-dependent kinase inhibitor 3), a dual specificity protein phosphatase, dephosphorylates cyclin-dependent kinases (CDKs) and thus functions as a key negative regulator of cell cycle progression. Deregulation or mutations of CDNK3 have been implicated in various cancers. However, the role of CDKN3 in Bcr-Abl-mediated chronic myelogenous leukemia (CML) remains unknown. Here we found that CDKN3 acts as a tumor suppressor in Bcr-Abl-mediated leukemogenesis. Overexpression of CDKN3 sensitized the K562 leukemic cells to imanitib-induced apoptosis and dramatically inhibited K562 xenografted tumor growth in nude mouse model. Ectopic expression of CDKN3 significantly reduced the efficiency of Bcr-Abl-mediated transformation of FDCP1 cells to growth factor independence. In contrast, depletion of CDKN3 expression conferred resistance to imatinib-induced apoptosis in the leukemic cells and accelerated the growth of xenograph leukemia in mice. In addition, we found that CDKN3 mutant (CDKN3-C140S) devoid of the phosphatase activity failed to affect the K562 leukemic cell survival and xenografted tumor growth, suggesting that the phosphatase of CDKN3 was required for its tumor suppressor function. Furthermore, we observed that overexpression of CDKN3 reduced the leukemic cell survival by dephosphorylating CDK2, thereby inhibiting CDK2-dependent XIAP expression. Moreover, overexpression of CDKN3 delayed G1/S transition in K562 leukemic cells. Our results highlight the importance of CDKN3 in Bcr-Abl-mediated leukemogenesis, and provide new insights into diagnostics and therapeutics of the leukemia.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

SAB4501043
Anti-ABL antibody produced in rabbit, affinity isolated antibody
HPA027251
Anti-ABL1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution, Ab1
HPA027280
Anti-ABL1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution, Ab2
HPA028409
Anti-ABL1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
SAB4501046
Anti-ABL1 antibody produced in rabbit, affinity isolated antibody
SAB1405469
Anti-BIRC4 antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
SAB1411890
ANTI-BIRC4 antibody produced in rabbit, purified immunoglobulin, buffered aqueous solution
AV01008 Anti-CDK2 (AB1) antibody produced in rabbit, IgG fraction of antiserum
AV03006
Anti-CDK2 (AB2) antibody produced in rabbit, IgG fraction of antiserum
C5223 Anti-Cdk2 antibody produced in rabbit, IgG fraction of antiserum, buffered aqueous glycerol solution
SAB4503706
Anti-CDK2 antibody produced in rabbit, affinity isolated antibody
SAB4300110
Anti-phospho-CDK2 (pThr160) antibody produced in rabbit, affinity isolated antibody
SAB4504362
Anti-phospho-CDK2 (pThr160) antibody produced in rabbit, affinity isolated antibody
X4503 Anti-XIAP antibody produced in goat, affinity isolated antibody, lyophilized powder
PRS3331
Anti-XIAP antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
SAB4501453
Anti-XIAP antibody produced in rabbit, affinity isolated antibody
SAB5300355
Monoclonal Anti-ABL1 antibody produced in mouse, clone 7B11D6, ascites fluid
WH0000331M1
Monoclonal Anti-BIRC4 antibody produced in mouse, clone 2B3, purified immunoglobulin, buffered aqueous solution
SAB1403557
Monoclonal Anti-BIRC4 antibody produced in mouse, clone 1F4, purified immunoglobulin, buffered aqueous solution
A5844 Monoclonal Anti-c-Abl antibody produced in mouse, clone ABL-148, ascites fluid
WH0001017M2
Monoclonal Anti-CDK2 antibody produced in mouse, clone 2E8, purified immunoglobulin, buffered aqueous solution
SAB5300328
Monoclonal Anti-CDK2 antibody produced in mouse, clone 1A6, purified immunoglobulin, buffered aqueous solution
PLA0213
Rabbit anti-CDK2 Antibody, Affinity Purified, Powered by Bethyl Laboratories, Inc.