The cyclin D1-CDK4 oncogenic interactome enables identification of potential novel oncogenes and clinical prognosis

被引：25

作者：

Jirawatnotai, Siwanon ^{[1
]}

Sharma, Samanta ^{[2
,3
]}

Michowski, Wojciech ^{[2
,3
]}

Suktitipat, Bhoom ^{[4
]}

Geng, Yan ^{[2
,3
]}

Quackenbush, John ^{[5
]}

Elias, Joshua E. ^{[6
]}

Gygi, Steven P. ^{[7
]}

Wang, Yaoyu E. ^{[5
]}

Sicinski, Piotr ^{[2
,3
]}

机构：

[1] Mahidol Univ, Siriraj Hosp, Fac Med, Dept Pharmacol, Bangkok 10700, Thailand

[2] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA

[4] Mahidol Univ, Siriraj Hosp, Fac Med, Dept Biochem, Bangkok 10700, Thailand

[5] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Ctr Canc Computat Biol, Boston, MA 02115 USA

[6] Stanford Univ, Dept Chem & Syst Biol, Stanford, CA 94305 USA

[7] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA

来源：

CELL CYCLE | 2014年 / 13卷 / 18期

关键词：

breast cancer; CDK4; cyclin D1; interactome; oncogenes; oncogenic signature; BREAST-CANCER; D1; PROTEIN; GENE; EXPRESSION; OVEREXPRESSION; AMPLIFICATION; HSP90; IRTKS; CDC37;

D O I：

10.4161/15384101.2014.946850

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Overexpression of cyclin D1 and its catalytic partner, CDK4, is frequently seen in human cancers. We constructed cyclin D1 and CDK4 protein interaction network in a human breast cancer cell line MCF7, and identified novel CDK4 protein partners. Among CDK4 interactors we observed several proteins functioning in protein folding and in complex assembly. One of the novel partners of CDK4 is FKBP5, which we found to be required to maintain CDK4 levels in cancer cells. An integrative analysis of the extended cyclin D1 cancer interactome and somatic copy number alterations in human cancers identified BAIAPL21 as a potential novel human oncogene. We observed that in several human tumor types BAIAPL21 is expressed at higher levels as compared to normal tissue. Forced overexpression of BAIAPL21 augmented anchorage independent growth, increased colony formation by cancer cells and strongly enhanced the ability of cells to form tumors in vivo. Lastly, we derived an Aggregate Expression Score (AES), which quantifies the expression of all cyclin D1 interactors in a given tumor. We observed that AES has a prognostic value among patients with ER-positive breast cancers. These studies illustrate the utility of analyzing the interactomes of proteins involved in cancer to uncover potential oncogenes, or to allow better cancer prognosis.

引用

页码：2889 / 2900

页数：12

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