Interactions between activating signal cointegrator-2 and the tumor suppressor retinoblastoma in androgen receptor transactivation.
Activating signal cointegrator-2 (ASC-2), a cancer-amplified transcription coactivator of nuclear receptors and numerous other transcription factors, was previously shown to contain two LXXLL motifs, each of which interacts with a distinct set of nuclear receptors. In this work, we showed that ASC-2 has an indirect, separate binding site for androgen receptor (AR). Interestingly, this region overlapped with the direct interaction interfaces with the tumor suppressor retinoblastoma (Rb). Although ASC-2 alone stimulated AR transactivation in cotransfections of HeLa cells, ectopic expression of Rb effected ASC-2 to act as a transcription coactivator of AR in Rb-null Saos2 cells. These results, along with the previous report in which AR was shown to directly interact with Rb (Yeh, S., Miyamoto, H., Nishimura, K., Kang, H., Ludlow, J., Hsiao, P., Wang, C., Su, C., and Chang C. (1998) Biochem. Biophys. Res. Commun. 248, 361-367), suggest that the AR-ASC-2 interactions in vivo may involve Rb. Thus, ASC-2 appears to contain at least three distinct nuclear receptor interaction domains.
Goo
Young-Hwa
YH
Division of Diabetes, Endocrinology & Metabolism, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
Na
Soon-Young
SY
Zhang
Hao
H
Xu
Jianming
J
Hong
SunHwa
S
Cheong
JaeHun
J
Lee
Soo-Kyung
SK
Lee
Jae Woon
JW
D020816:Amino Acid Motifs; D000818:Animals; D002843:Chromatin / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D049452:Green Fluorescent Proteins; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins / Q000378:metabolism; D056918:Nuclear Receptor Coactivators; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation
D002843:Chromatin; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; C486559:NCOA6 protein, human; D056918:Nuclear Receptor Coactivators; D011944:Receptors, Androgen; D011993:Recombinant Fusion Proteins; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D005982:Glutathione Transferase