Knockdown of human deubiquitinase PSMD14 induces cell cycle arrest and senescence
| Autor: | Joseph Gans, Rajashree McLaren, Yide Jiang, Kara Carter, Beverly A. Teicher, Stephen L. Madden, Michael Booker, Yinyin Huang, Tatiana Gladysheva, Beirong Liang, Mark A. Goldberg, Paul T. Mason, Mindy Zhang, Hans-Peter Biemann, James Lillie, Lilly Chai, Katherine W. Klinger, Ann Byrne, Michael R. Dufault |
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| Rok vydání: | 2010 |
| Předmět: |
Proteasome Endopeptidase Complex
Cell Survival Cyclin A Gene Expression Transfection Resting Phase Cell Cycle Retinoblastoma Protein Cell Line Tumor CDC2 Protein Kinase Humans cdc25 Phosphatases Cyclin D1 Cyclin B1 Phosphorylation RNA Small Interfering Cellular Senescence Cell Proliferation Cyclin-Dependent Kinase Inhibitor Proteins biology PSMD14 Cell Cycle G1 Phase Retinoblastoma protein Epithelial Cells DNA Cell Biology Fibroblasts Cell cycle beta-Galactosidase Ubiquitinated Proteins Up-Regulation Cell biology PSMB5 Trans-Activators biology.protein Cancer research Sulfotransferases Cell aging HeLa Cells Cyclin-dependent kinase inhibitor protein |
| Zdroj: | Experimental Cell Research. 316:258-271 |
| ISSN: | 0014-4827 |
| DOI: | 10.1016/j.yexcr.2009.08.018 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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