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Tip60 is a co-activator specific for class I nuclear hormone receptors

Lookup NU author(s): Dr Luke Gaughan, Mark Brady, Susan Cook, Professor David Neal, Professor Craig Robson

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Abstract

The nuclear hormone receptor superfamily is composed of a group of hormone-dependent transcription factors that play prominent roles in homeostatic events in vertebrates. A prerequisite for steroid hormone receptor activity is the binding of co-activator molecules to the activation function-2 domain of the receptor. The LXXLL motif/nuclear receptor box, contained within a number of co-activator molecules, mediates the interaction with nuclear hormone receptors. Tip60 (Tat-interactive protein 60 kDa), previously shown to bind to and enhance androgen receptor (AR)-mediated transactivation, contains a single nuclear receptor box at its extreme C terminus. We demonstrate that unlike members of the p160 co-activator family that interact predominantly with the N terminus of the AR in an LXXLL motif-independent manner, the LXXLL motif of Tip60 is required and is sufficient for AR interaction. Furthermore, by using the mammalian two-hybrid system and transient transfection experiments, we show that Tip60 preferentially interacts with and up-regulates class I nuclear receptors, suggesting that Tip60 is a steroid hormone receptor-specific co-activator. We conclude that Tip60 may specifically regulate a subset of nuclear hormone receptors, giving an indication to how regulated nuclear receptor activation can be achieved.


Publication metadata

Author(s): Gaughan, L., Brady, M. E., Cook, S., Neal, D. E., Robson, C. N.

Publication type: Article

Publication status: Published

Journal: Journal of Biological Chemistry

Year: 2001

Volume: 276

Issue: 50

Pages: 46841-46848

ISSN (print): 0021-9258

ISSN (electronic): 1083-351X

URL: http://dx.doi.org/10.1074/jbc.M103710200

DOI: 10.1074/jbc.M103710200


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