Androgen via p21 inhibits tumor necrosis factor alpha-induced JNK activation and apoptosis.
The male hormone androgen is a growth/survival factor for its target tissues or organs. Yet, the underlying mechanism is incompletely understood. Here, we report that androgen via p21 inhibits tumor necrosis factor alpha-induced JNK activation and apoptosis. Inhibition by androgen requires the transcription activity of androgen receptor (AR) and de novo protein synthesis. Androgen.AR induces expression of p21 that in turn inhibits tumor necrosis factor alpha-induced JNK and apoptosis. Furthermore, genetic interruption of p21 alleles abolishes the inhibition by androgen. Our results reveal a novel cross-talk between androgen x AR and JNK, thereby providing a molecular mechanism underlying the survival function of androgen.
Tang
Fangming
F
Ben May Department for Cancer Research, University of Chicago, Chicago, Illinois 60637, USA.
Kokontis
John
J
Lin
Yuting
Y
Liao
Shutsung
S
Lin
Anning
A
Xiang
Jialing
J
D000483:Alleles; D000728:Androgens / Q000378:metabolism*; D017209:Apoptosis; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D004789:Enzyme Activation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D011471:Prostatic Neoplasms / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
C410798:AR protein, human; D000728:Androgens; D050759:Cyclin-Dependent Kinase Inhibitor p21; D011944:Receptors, Androgen; D014409:Tumor Necrosis Factor-alpha; D048670:MAP Kinase Kinase 4