Abstract
The SMRT corepressor complex participates in transcriptional repression by a diverse array of vertebrate transcription factors. The ability to recruit SMRT appears to play a crucial role in leukemogenesis by the PML-retinoic acid receptor α (RARα) oncoprotein, an aberrant nuclear hormone receptor implicated in human acute promyelocytic leukemia (APL). Arsenite induces clinical remission of APL through a incompletely understood mechanism. We report here that arsenite is a potent inhibitor of the interaction of SMRT with its transcription factor partners, including PML-RARα. Arsenite operates, in part, through a mitogen-activated protein (MAP) kinase cascade culminating in phosphorylation of the SMRT protein, dissociation of SMRT from its nuclear receptor partners, and a relocalization of SMRT out of the nucleus into the cytoplasm of the cell. Conversely, inhibition of this MAP kinase cascade attenuates the effects of arsenite on APL cells. Our results implicate SMRT as an important biological target for the actions of arsenite in both normal and neoplastic cells.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 7172-7182 |
| Number of pages | 11 |
| Journal | Molecular and Cellular Biology |
| Volume | 21 |
| Issue number | 21 |
| DOIs | |
| State | Published - 2001 |
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ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cell Biology
Cite this
Arsenic trioxide is a potent inhibitor of the interaction of SMRT corepressor with its transcription factor partners, including the PML-retinoic acid receptor α oncoprotein found in human acute promyelocytic leukemia. / Hong, S. H.; Yang, Z.; Privalsky, M. L.
In: Molecular and Cellular Biology, Vol. 21, No. 21, 2001, p. 7172-7182.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Arsenic trioxide is a potent inhibitor of the interaction of SMRT corepressor with its transcription factor partners, including the PML-retinoic acid receptor α oncoprotein found in human acute promyelocytic leukemia
AU - Hong, S. H.
AU - Yang, Z.
AU - Privalsky, M. L.
PY - 2001
Y1 - 2001
N2 - The SMRT corepressor complex participates in transcriptional repression by a diverse array of vertebrate transcription factors. The ability to recruit SMRT appears to play a crucial role in leukemogenesis by the PML-retinoic acid receptor α (RARα) oncoprotein, an aberrant nuclear hormone receptor implicated in human acute promyelocytic leukemia (APL). Arsenite induces clinical remission of APL through a incompletely understood mechanism. We report here that arsenite is a potent inhibitor of the interaction of SMRT with its transcription factor partners, including PML-RARα. Arsenite operates, in part, through a mitogen-activated protein (MAP) kinase cascade culminating in phosphorylation of the SMRT protein, dissociation of SMRT from its nuclear receptor partners, and a relocalization of SMRT out of the nucleus into the cytoplasm of the cell. Conversely, inhibition of this MAP kinase cascade attenuates the effects of arsenite on APL cells. Our results implicate SMRT as an important biological target for the actions of arsenite in both normal and neoplastic cells.
AB - The SMRT corepressor complex participates in transcriptional repression by a diverse array of vertebrate transcription factors. The ability to recruit SMRT appears to play a crucial role in leukemogenesis by the PML-retinoic acid receptor α (RARα) oncoprotein, an aberrant nuclear hormone receptor implicated in human acute promyelocytic leukemia (APL). Arsenite induces clinical remission of APL through a incompletely understood mechanism. We report here that arsenite is a potent inhibitor of the interaction of SMRT with its transcription factor partners, including PML-RARα. Arsenite operates, in part, through a mitogen-activated protein (MAP) kinase cascade culminating in phosphorylation of the SMRT protein, dissociation of SMRT from its nuclear receptor partners, and a relocalization of SMRT out of the nucleus into the cytoplasm of the cell. Conversely, inhibition of this MAP kinase cascade attenuates the effects of arsenite on APL cells. Our results implicate SMRT as an important biological target for the actions of arsenite in both normal and neoplastic cells.
UR - http://www.scopus.com/inward/record.url?scp=0034786069&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034786069&partnerID=8YFLogxK
U2 - 10.1128/MCB.21.21.7172-7182.2001
DO - 10.1128/MCB.21.21.7172-7182.2001
M3 - Article
C2 - 11585900
AN - SCOPUS:0034786069
VL - 21
SP - 7172
EP - 7182
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
SN - 0270-7306
IS - 21
ER -