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XB-ART-11957
J Biol Chem. November 26, 1999; 274 (48): 34283-93.

A nuclear factor, ASC-2, as a cancer-amplified transcriptional coactivator essential for ligand-dependent transactivation by nuclear receptors in vivo.

Lee SK , Anzick SL , Choi JE , Bubendorf L , Guan XY , Jung YK , Kallioniemi OP , Kononen J , Trent JM , Azorsa D , Jhun BH , Cheong JH , Lee YC , Meltzer PS , Lee JW .


Abstract
Many transcription coactivators interact with nuclear receptors in a ligand- and C-terminal transactivation function (AF2)-dependent manner. We isolated a nuclear factor (designated ASC-2) with such properties by using the ligand-binding domain of retinoid X receptor as a bait in a yeast two-hybrid screening. ASC-2 also interacted with other nuclear receptors, including retinoic acid receptor, thyroid hormone receptor, estrogen receptor alpha, and glucocorticoid receptor, basal factors TFIIA and TBP, and transcription integrators CBP/p300 and SRC-1. In transient cotransfections, ASC-2, either alone or in conjunction with CBP/p300 and SRC-1, stimulated ligand-dependent transactivation by wild type nuclear receptors but not mutant receptors lacking the AF2 domain. Consistent with an idea that ASC-2 is essential for the nuclear receptor function in vivo, microinjection of anti-ASC-2 antibody abrogated the ligand-dependent transactivation of retinoic acid receptor, and this repression was fully relieved by coinjection of ASC-2-expression vector. Surprisingly, ASC-2 was identical to a gene previously identified during a search for genes amplified and overexpressed in breast and other human cancers. From these results, we concluded that ASC-2 is a bona fide transcription coactivator molecule of nuclear receptors, and its altered expression may contribute to the development of cancers.

PubMed ID: 10567404
Article link: J Biol Chem.

Genes referenced: crebbp ep300 gtf2a1 ncoa1 nr3c1 pycard src sts tbp
Antibodies referenced:
Morpholinos referenced:

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