Abstract
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.
Highlights
MBP-1, an,37 kDa cellular protein, has multiple functions
To investigate the role of endogenous MBP-1 in cellular proliferation, we knocked down endogenous MBP-1 in human foreskin fibroblasts (HFF) using RNA interference
We examined whether knockdown of MBP-1 modulates cell cycle progression in HFF-MBPsi-4 by FACS analysis
Summary
MBP-1, an ,37 kDa cellular protein, has multiple functions. It binds to the c-myc promoter sequences and transcriptionally represses the c-myc gene. MBP-1 acts as a general transcriptional repressor [1,2,3]. Sequence analysis suggested that MBP-1 has a high homology with ENO1 cDNA, an ,48 kDa protein, designated as human enolase cDNA [1, 4]. Whether full length ENO1 gene product has a similar function like MBP-1 in carcinoma cells is yet to be determined. While the role of exogenous expression of MBP-1 in the transcription and cell growth regulation appear to be established, the in vivo function of this protein is poorly understood
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