Zeuspaul, Speaking of credibility, look at the current issue of Nature. LGND exclusive consultant, scientific founder, and head of Scientific Advisory Board, Ron Evans, has a major paper on a cofactor that influences the action of retinoids as will as factors that will modulate this activity:
Role of the histone deacetylase complex in acute promyelocytic
leukaemia
Non-liganded retinoic acid receptors (RARs) repress transcription of target
genes by recruiting the histone deacetylase complex through a class of
silencing mediators termed SMRT or N-CoR. Mutant forms of RAR-alpha,
created by chromosomal translocations with either the PML (for
promyelocytic leukaemia) or the PLZF (for promyelocytic leukaemia zinc
finger), locus, are oncogenic and result in human acute promyelocytic
leukaemia (APL). PML-RAR-alpha APL patients achieve complete
remission following treatments with pharmacological doses of retinoic acids
(RA); in contrast, PLZF-RAR-alpha patients respond very poorly, if at all.
Here the authors report that the association of these two chimaeric receptors
with the histone deacetylase (HDAC) complex helps to determine both the
development of APL and the ability of patients to respond to retinoids.
Consistent with these observations, inhibitors of histone deacetylase
dramatically potentiate retinoid-induced differentiation of RA-sensitive, and
restore retinoid responses of RA-resistant, APL cell lines. The authors'
findings suggest that oncogenic RARs mediate leukaemogenesis through
aberrant chromatin acetylation, and that pharmacological manipulation of
nuclear receptor co-factors may be a useful approach in the treatment of
human disease.
R J Lin, L Nagy, S Inoue, W Shao, W H Miller Jr & R M Evans
Role of the histone deacetylase complex in acute promyelocytic
leukaemia (Letter to Nature)
Nature 391, 811 (1998) |
