Activating signal cointegrator 1 is highly expressed in murine testicular Leydig cells and enhances the ligand-dependent transactivation of androgen receptor.
Activating signal cointegrator 1 (ASC-1) has been recently reported as a coactivator of some nuclear receptors. In the present study, we have analyzed the expression of ASC-1 in the mouse testis and investigated its capacity to modulate the transcriptional activity of androgen receptor (AR). We found that although ASC-1 mRNA was ubiquitously expressed at a low level in mouse tissues, a couple of testis-specific mRNAs were expressed in the adult testis. Cloning of one testis-specific variant revealed that the ubiquitous and testis-specific transcripts of ASC-1 share at least the same open reading frame. The expression of the testis-specific ASC-1 mRNAs was developmentally regulated, and the onset of their expression coincided with the initiation of spermatogenesis. In situ hybridization of mouse testis with ASC-1 antisense probe demonstrated predominant expression of ASC-1 in the interstitial Leydig cells that express AR. Moreover, yeast two-hybrid tests and glutathione S-transferase pull-down assays revealed that ASC-1 associates directly with AR and that the hinge domain of AR and a putative zinc-finger motif of ASC-1 are major determinants for their interaction. Transient transfection assays performed by expressing ASC-1 in combination with AR and an androgen-responsive reporter gene showed that ASC-1 moderately alters the induction of the reporter gene. Taken together, these results suggest that ASC-1 may function as an AR coregulator and have a role in testicular functions.
Lee
Yong Soo
YS
Hormone Research Center, Chonnam National University, Gwangju 500-757, Republic of Korea.
Kim
Hyun-Jin
HJ
Lee
Hyun Ju
HJ
Lee
Jae Woon
JW
Chun
Sang-Young
SY
Ko
Sun-Kun
SK
Lee
Keesook
K
D000818:Animals; D002478:Cells, Cultured; D003001:Cloning, Molecular; D006801:Humans; D007985:Leydig Cells / Q000166:cytology / Q000378:metabolism*; D008024:Ligands; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009928:Organ Specificity; D011485:Protein Binding / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D012741:Sexual Maturation / Q000502:physiology; D013737:Testis / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques; D016335:Zinc Fingers
D008024:Ligands; D012333:RNA, Messenger; D011944:Receptors, Androgen; D014157:Transcription Factors; C459902:Trip4 protein, mouse