Abstract |
Retinoic acid receptor (RA) heterodimer (RAR/RXR) activities have been shown to be repressed by transcriptional co-repressor, SMRT/N-CoR, in the absence of the ligand while upon all-trans retionic acid (ATRA) treatment, SMRT/N-CoR is dissociated from RARalpha leading to gene expression by the recruitment of transcriptional co-activators to the transcriptional complex. The difference in response to ATRA therapy between acute promyelocytic leukemia (APL) patients with PML-RARalpha fusion and PLZF-RARalpha fusion has recently been found to be partially due to the strong association of the transcriptional co-repressor, SMRT/N-CoR, with PLZF domain. We demonstrate that SMRT association, as with PML-RARalpha, can be released from NPM-RARalpha at pharmacological concentration of ATRA (10-6 M). Moreover, we show for the first time that the interaction between the transcriptional co-activator, RIP-140, and PML-, PLZF- or NPM-RARalpha fusion proteins can be positively stimulated by ATRA although they are less sensitive as compared with the wild-type RARalpha. Our results suggest that the dissociation of transcriptional co-repressors, SMRT/N-CoR, and recruitment of co-activators, eg RIP-140, to APL-associated fusion proteins constitute a common molecular mechanism in APL and underlie the responsiveness of the disease to RA therapy. Leukemia (2000) 14, 77-83.
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Authors | C W So, S Dong, C K So, G X Cheng, Q H Huang, S J Chen, L C Chan |
Journal | Leukemia
(Leukemia)
Vol. 14
Issue 1
Pg. 77-83
(Jan 2000)
ISSN: 0887-6924 [Print] England |
PMID | 10637480
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- NPM-RARalpha protein, human
- Neoplasm Proteins
- Oncogene Proteins, Fusion
- PLZF-RARalpha fusion protein, human
- Trans-Activators
- promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein
- Tretinoin
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Topics |
- Dimerization
- Humans
- Leukemia, Promyelocytic, Acute
(drug therapy, metabolism)
- Neoplasm Proteins
(metabolism)
- Oncogene Proteins, Fusion
(metabolism)
- Protein Binding
- Trans-Activators
(metabolism)
- Tretinoin
(therapeutic use)
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