Article: The impact of differential binding of wild-type RARA, PML-, PLZF- and NPM-RARA fusion proteins towards transcriptional co-activator, RIP-140, on retinoic acid responses in acute promyelocytic leukemia

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TitleThe impact of differential binding of wild-type RARA, PML-, PLZF- and NPM-RARA fusion proteins towards transcriptional co-activator, RIP-140, on retinoic acid responses in acute promyelocytic leukemia
AuthorsSo, CW1
Dong, S2
So, CKC1
Cheng, GX2
Huang, QH3
Chen, SJ3
Chan, LC1
Issue Date2000
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/leu
CitationLeukemia, 2000, v. 14 n. 1, p. 77-83 [How to Cite?]
AbstractRetinoic 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 RARA(U 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-RARA(U fusion and PLZF-RARA 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-RARA, can be released from NPM-RARA 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-RARA fusion proteins can be positively stimulated by ATRA although they are less sensitive as compared with the wild-type RARA. 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.
ISSN0887-6924
2011 Impact Factor: 9.561
2011 SCImago Journal Rankings: 1.237
ISI Accession Number IDWOS:000084925300011
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorSo, CW
dc.contributor.authorDong, S
dc.contributor.authorSo, CKC
dc.contributor.authorCheng, GX
dc.contributor.authorHuang, QH
dc.contributor.authorChen, SJ
dc.contributor.authorChan, LC
dc.date.accessioned2012-05-29T06:11:23Z
dc.date.available2012-05-29T06:11:23Z
dc.date.issued2000
dc.description.abstractRetinoic 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 RARA(U 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-RARA(U fusion and PLZF-RARA 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-RARA, can be released from NPM-RARA 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-RARA fusion proteins can be positively stimulated by ATRA although they are less sensitive as compared with the wild-type RARA. 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.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationLeukemia, 2000, v. 14 n. 1, p. 77-83 [How to Cite?]
dc.identifier.epage83
dc.identifier.isiWOS:000084925300011
dc.identifier.issn0887-6924
2011 Impact Factor: 9.561
2011 SCImago Journal Rankings: 1.237
dc.identifier.issue1
dc.identifier.pmid10637480
dc.identifier.scopuseid_2-s2.0-0033964844
dc.identifier.spage77
dc.identifier.urihttp://hdl.handle.net/10722/148192
dc.identifier.volume14
dc.languageeng
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/leu
dc.publisher.placeUnited Kingdom
dc.relation.ispartofLeukemia
dc.relation.referencesReferences in Scopus
dc.subject.meshDimerization
dc.subject.meshHumans
dc.subject.meshLeukemia, Promyelocytic, Acute - Drug Therapy - Metabolism
dc.subject.meshNeoplasm Proteins - Metabolism
dc.subject.meshOncogene Proteins, Fusion - Metabolism
dc.subject.meshProtein Binding
dc.subject.meshTrans-Activators - Metabolism
dc.subject.meshTretinoin - Therapeutic Use
dc.titleThe impact of differential binding of wild-type RARA, PML-, PLZF- and NPM-RARA fusion proteins towards transcriptional co-activator, RIP-140, on retinoic acid responses in acute promyelocytic leukemia
dc.typeArticle
Author Affiliations
  1. The University of Hong Kong
  2. Shanghai Transgenic Research Center
  3. Shanghai Second Medical University