GRIP1 mediates the interaction between the amino- and carboxyl-termini of the androgen receptor
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Howard C. Shen
Abstract
The androgen receptor (AR) mediates transactivation of target genes by acting as a dimer in which its amino-terminal domain (AR-NTD) interacts with its carboxyl-terminal, ligand-binding domain (AR-LBD) (N/C interaction). Here we assessed if and how AR N/C interaction relates to AR transactivation activity and how the p160 coactivator GRIP1 participates in both processes. The concentration of dihydrotestosterone needed for half-maximal N/C interaction was approximately 10-fold higher than for half-maximal transactivation, indicating a disparity between the two processes. Although a mutation of an LXXLL-like motif, 23FQNLF27→23FQNAA27, in the AR-NTD abolished AR N/C interaction, it could be restored by the co-expression of the coactivator GRIP1. Co-expression of mutated forms of GRIP1, possessing alterations known to abolish either of the two AR interaction domains, could not restore AR N/C interaction, suggesting that wild-type GRIP1 normally bridges the two AR domains. Although AR transactivation activity can proceed without AR N/C interaction, we propose that part of the GRIP1 coactivation activity resides in its ability to bind both AR-NTD and -LBD, to stabilize the N/C complex and allow for secondary cofactors to be recruited more efficiently. Our results also indicate that AR N/C interaction enhances but is not necessary for AR transactivation activity.
References
Doesburg, P., Kuil, C.W., Berrevoets, C.A., Steketee, K., Faber, P.W., Mulder, E., Brinkmann, A.O., and Trapman, J. (1997). Functional in vivo interaction between the amino-terminal, transactivation domain and the ligand binding domain of the androgen receptor. Biochemistry36, 1052–1064.10.1021/bi961775gSuche in Google Scholar
Gelmann, E.P. (2002). Molecular biology of the androgen receptor. J. Clin. Oncol.20, 3001–3015.10.1200/JCO.2002.10.018Suche in Google Scholar
He, B., and Wilson, E.M. (2002). The NH2-terminal and carboxyl-terminal interaction in the human androgen receptor. Mol. Genet. Metab.75, 293–298.10.1016/S1096-7192(02)00009-4Suche in Google Scholar
He, B., Bowen, N.T., Minges, J.T., and Wilson, E.M. (2001). Androgen-induced NH2- and COOH-terminal interaction inhibits p160 coactivator recruitment by activation function 2. J. Biol. Chem.276, 42293–42301.10.1074/jbc.M107492200Suche in Google Scholar
He, B., Lee, L.W., Minges, J.T., and Wilson, E.M. (2002). Dependence of selective gene activation on the androgen receptor NH2- and COOH-terminal interaction. J. Biol. Chem.277, 25631–25639.10.1074/jbc.M202809200Suche in Google Scholar
Ikonen, T., Palvimo, J.J., and Janne, O.A. (1997). Interaction between the amino- and carboxyl-terminal regions of the rat androgen receptor modulates transcriptional activity and is influenced by nuclear receptor coactivators. J. Biol. Chem.272, 29821–29828.10.1074/jbc.272.47.29821Suche in Google Scholar
Irvine, R.A., Ma, H., Yu, M.C., Ross, R.K., Stallcup, M.R. and Coetzee, G.A. (2000). Inhibition of p160-mediated coactivation with increasing androgen receptor polyglutamine length. Hum. Mol. Genet.9, 267–274.10.1093/hmg/9.2.267Suche in Google Scholar
Kasper, S., Rennie, P.S., Bruchovsky, N., Lin, L., Cheng, H., Snoek, R., Dahlman-Wright, K., Gustafsson, J.A., Shiu, R.P., Sheppard, P.C., and Matusik, R.J. (1999). Selective activation of the probasin androgen-responsive region by steroid hormones. J. Mol. Endocrinol.22, 313–325.10.1677/jme.0.0220313Suche in Google Scholar
Ma, H., Hong, H., Huang, S.M., Irvine, R.A., Webb, P., Kushner, P.J., Coetzee, G.A., and Stallcup, M.R. (1999). Multiple signal input and output domains of the 160-kilodalton nuclear receptor coactivator proteins. Mol. Cell. Biol.19, 6164–6173.10.1128/MCB.19.9.6164Suche in Google Scholar
Snoek, R., Bruchovsky, N., Kasper, S., Matusik, R.J., Gleave, M., Sato, N., Mawji, N.R., and Rennie, P.S. (1998). Differential transactivation by the androgen receptor in prostate cancer cells. Prostate36, 256–263.10.1002/(SICI)1097-0045(19980901)36:4<256::AID-PROS7>3.0.CO;2-DSuche in Google Scholar
©2004 by Walter de Gruyter Berlin New York
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Artikel in diesem Heft
- The structure of the juvenile hormone binding protein gene from Galleria mellonella
- Interaction of thiamin diphosphate with phosphorylated and dephosphorylated mammalian pyruvate dehydrogenase complex
- Purification and characterization of a chitinase-like antifungal protein from black turtle bean with stimulatory effect on nitric oxide production by macrophages
- Nitric oxide covalently labels a 6-hydroxydopa-derived free radical intermediate in the catalytic cycle of copper/quinone-containing amine oxidase from lentil seedlings
- Plasmodium falciparum glutaredoxin-like proteins
- Characterization of the glyoxalases of the malarial parasite Plasmodium falciparum and comparison with their human counterparts
- Transcriptional down-regulation of neurotrophin-3 in chronic obstructive pulmonary disease
- Limb girdle muscular dystrophy in a sibling pair with a homozygous Ser606Leu mutation in the alternatively spliced IS2 region of calpain 3
- GRIP1 mediates the interaction between the amino- and carboxyl-termini of the androgen receptor
- Dual concentration-dependent activity of thyroglobulin type-1 domain of testican: specific inhibitor and substrate of cathepsin L
- Proteolysis of insulin-like growth factor binding proteins (IGFBPs) by calpain
