Exp Mol Med.  2009 Jun;41(6):429-439. 10.3858/emm.2009.41.6.048.

The orphan nuclear receptor SHP inhibits apoptosis during the monocytic differentiation by inducing p21WAF1

• Kim K
• Choi YH
• Kim HH
• Cheong J

• KMID: 756235
• DOI: http://doi.org/10.3858/emm.2009.41.6.048

Abstract

Small heterodimer partner (SHP) is an atypical member of nuclear receptor superfamily that lacks a DNA-binding domain. In previous study, we showed that SHP, c-jun, p65 of NF-kappaB subunits, and p21WAF1 expression was increased during monocytic differentiaton with the exposure of human leukemia cells to a differentiation agent, PMA. In this study, c-Jun and p65 were shown to mediate the transcriptional activation of the SHP promoter. In addition, SHP induced the cell cycle regulatory protein levels and cooperatively increased an induction of p21WAF1 expression with p65. Furthermore, SHP protected differentiated cells from etoposide-induced cellular apoptosis through the induction and cytoplasmic sequestration of p21WAF1. Complex formation between SHP and p21WAF1 was demonstrated by means of coimmunoprecipitation. These results suggest that SHP prolongs a cellular survival of differentiating monocytes through the transcriptional regulation of target genes of cell survival and differentiation.

Keyword

apoptosis; cell differentiation; cyclin-dependent kinase inhibitor p21; monocytes; nuclear receptor subfamily 0, group B, member 2

MeSH Terms

*Apoptosis
Cell Differentiation
Cell Line, Tumor
Cyclin-Dependent Kinase Inhibitor p21/genetics/*metabolism
Gene Expression Regulation
Humans
Monocytes/cytology
Promoter Regions, Genetic
Proto-Oncogene Proteins c-jun/genetics/metabolism
Receptors, Cytoplasmic and Nuclear/genetics/*metabolism
Transcription Factor RelA/genetics/metabolism