Here's another Evan's paper showing a similar synergy in another type of cancer (myeloid leukemia):
Cell 1997 May 2;89(3):373-380
Nuclear receptor repression mediated by a complex
containing SMRT, mSin3A, and histone deacetylase.
Nagy L, Kao HY, Chakravarti D, Lin RJ, Hassig CA, Ayer DE, Schreiber SL, Evans RM
The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
The transcriptional corepressors SMRT and N-CoR function as silencing mediators for retinoid and
thyroid hormone receptors. Here we show that SMRT and N-CoR directly interact with mSin3A, a
corepressor for the Mad-Max heterodimer and a homolog of the yeast global-transcriptional
repressor Sin3p. In addition, we demonstrate that the recently characterized histone deacetylase 1
(HDAC1) interacts with Sin3A and SMRT to form a multisubunit repressor complex. Consistent
with this model, we find that HDAC inhibitors synergize with retinoic acid to stimulate
hormone-responsive genes and differentiation of myeloid leukemia (HL-60) cells. This work
establishes a convergence of repression pathways for bHLH-Zip proteins and nuclear receptors and
suggests this type of regulation may be more widely conserved than previously suspected.
PMID: 9150137, UI: 97294381 |
