Knockdown of human deubiquitinase PSMD14 induces cell cycle arrest and senescence

被引：54

作者：

Byrne, Ann ^{[1
]}

McLaren, Rajashree A. ^{[1
]}

Mason, Paul ^{[1
]}

Chai, Lilly ^{[1
]}

Dufault, Michael R. ^{[1
]}

Huang, Yinyin ^{[1
]}

Liang, Beirong ^{[1
]}

Gans, Joseph D. ^{[1
]}

Zhang, Mindy ^{[1
]}

Carter, Kara ^{[1
]}

Gladysheva, Tatiana B. ^{[1
]}

Teicher, Beverly A. ^{[1
]}

Biemann, Hans-Peter N. ^{[1
]}

Booker, Michael ^{[1
]}

Goldberg, Mark A. ^{[1
]}

Klinger, Katherine W. ^{[1
]}

Lillie, James ^{[1
]}

Madden, Stephen L. ^{[1
]}

Jiang, Yide ^{[1
]}

机构：

[1] Genzyme Corp, Framingham, MA 01701 USA

来源：

EXPERIMENTAL CELL RESEARCH | 2010年 / 316卷 / 02期

关键词：

Proteasome; siRNA; PSMD14; PSMB5; pRb; p27(/Kip1); p21(/Cip1); Senescence; Cell arrest; KINASE INHIBITOR P27; 26S PROTEASOME; BORTEZOMIB RESISTANCE; TUMOR SUPPRESSION; DEGRADATION; UBIQUITIN; APOPTOSIS; CANCER; GENE; P27(KIP1);

D O I：

10.1016/j.yexcr.2009.08.018

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The PSMD14 (POH1, also known as Rpn11/MPR1/S13/CepP1) protein within the 19S complex (19S cap; PA700) is responsible for substrate deubiquitination during proteasomal degradation. The role of PSMD14 in cell proliferation and senescence was explored using siRNA knockdown in carcinoma cell lines. Our results reveal that down-regulation of PSMD14 by siRNA transfection had a considerable impact on cell viability causing cell arrest in the G0-G1 phase, ultimately leading to senescence. The molecular events associated with decreased cell proliferation, cell cycle arrest and senescence include down-regulation of cyclin B1-CDK1-CDC25C, down-regulation of cyclin D1 and up-regulation of p21(/Cip) and p27(/Kip1). Most notably, phosphorylation of the retinoblastoma protein was markedly reduced in PSMD14 knockdown cells. A comparative study with PSMB5, a subunit of the 20S proteasome, revealed that PSMB5 and PSMD14 have different effects on cell cycle, senescence and associated molecular events. These data support the view that the 19S and 20S subunits of the proteasome have distinct biological functions and imply that targeting 19S and 20S would have distinct molecular consequences on tumor cells. (C) 2009 Elsevier Inc. All rights reserved.

引用

页码：258 / 271

页数：14

共 43 条

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