Knockdown of MBP-1 in Human Foreskin Fibroblasts Induces p53-p21 Dependent Senescence

被引：11
作者：
Ghosh, Asish K. [1 ]
Kanda, Tatsuo [1 ]
Steele, Robert [1 ]
Ray, Ratna B. [1 ,2 ]
机构：
[1] St Louis Univ, Dept Pathol, St Louis, MO USA
[2] St Louis Univ, Canc Ctr, St Louis, MO USA
来源：
PLOS ONE | 2008年 / 3卷 / 10期
基金：
美国国家卫生研究院;
关键词：
D O I：
10.1371/journal.pone.0003384
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
MBP-1 acts as a general transcriptional repressor. Overexpression of MBP-1 induces cell death in a number of cancer cells and regresses tumor growth. However, the function of endogenous MBP-1 in normal cell growth regulation remains unknown. To unravel the role of endogenous MBP-1, we knocked down MBP-1 expression in primary human foreskin fibroblasts (HFF) by RNA interference. Knockdown of MBP-1 in HFF (HFF-MBPsi-4) resulted in an induction of premature senescence, displayed flattened cell morphology, and increased senescence-associated beta-galactosidase activity. FACS analysis of HFF-MBPsi-4 revealed accumulation of a high number of cells in the G1-phase. A significant upregulation of cyclin D1 and reduction of cyclin A was detected in HFF-MBPsi-4 as compared to control HFF. Senescent fibroblasts exhibited enhanced expression of phosphorylated and acetylated p53, and cyclin-dependent kinase inhibitor, p21. Further analysis suggested that promyolocytic leukemia protein (PML) bodies are dramatically increased in HFF-MBPsi-4. Together, these results demonstrated that knockdown of endogenous MBP-1 is involved in cellular senescence of HFF through p53-p21 pathway.
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