Activating signal cointegrator 1, a novel transcription coactivator of nuclear receptors, and its cytosolic localization under conditions of serum deprivation

Activating signal cointegrator 1 (ASC-1) harbors an autonomous transactivat ion domain that contains a putative zinc finger motif which provides bindin g sites for basal transcription factors TBP and TFIIA, transcription integr ators steroid receptor coactivator 1 (SRC-1) and CBP-p300, and nuclear rece ptors, as demonstrated by the glutathione S-transferase pull-delta assays a nd the yeast two-hybrid tests. The ASC-1 binding sites involve the hinge do main but not the C-terminal AF2 core domain of nuclear receptors. Nonethele ss, ASC-1 appears to require the AF2-dependent factors to function (i.e., C BP-p300 and SRC-1), as suggested by the ability of ASC-1 to coactivate nucl ear receptors, either alone or in cooperation with SRC-1 and p300, as well as its inability to coactivate a mutant receptor lacking the AF2 core domai n. By using indirect immunofluorescence, we further show that ASC-1, a nucl ear protein, is localized to the cytoplasm under conditions of serum depriv ation but is retained in the nucleus when it is serum starved in the presen ce of ligand or coexpressed CBP or SRC-1. These results suggest that ASC-1 is a novel coactivator molecule of nuclear receptors which functions in con junction with CBP-p300 and SRC-1 and may play an important role in establis hing distinct coactivator complexes under different cellular conditions.