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Article: HEXIM1 controls P-TEFb processing and regulates drug sensitivity in triple-negative breast cancer

TitleHEXIM1 controls P-TEFb processing and regulates drug sensitivity in triple-negative breast cancer
Authors
Issue Date2020
Citation
Molecular Biology of the Cell, 2020, v. 31, n. 17, p. 1867-1878 How to Cite?
AbstractThe positive transcription elongation factor b (P-TEFb), composed of CDK9 and cyclin T, stimulates transcriptional elongation by RNA polymerase (Pol) II and regulates cell growth and differentiation. Recently, we demonstrated that P-TEFb also controls the expression of EMT regulators to promote breast cancer progression. In the nucleus, more than half of P-TEFb are sequestered in the inactive-state 7SK snRNP complex. Here, we show that the assembly of the 7SK snRNP is preceded by an intermediate complex between HEXIM1 and P-TEFb that allows transfer of the kinase active P-TEFb from Hsp90 to 7SK snRNP for its suppression. Down-regulation of HEXIM1 locks P-TEFb in the Hsp90 complex, keeping it in the active state to enhance breast cancer progression, but also rendering the cells highly sensitive to Hsp90 inhibition. Because HEXIM1 is often down-regulated in human triple-negative breast cancer (TNBC), these cells are particularly sensitive to Hsp90 inhibition. Our study provides a mechanistic explanation for the increased sensitivity of TNBC to Hsp90 inhibition.
Persistent Identifierhttp://hdl.handle.net/10722/324142
ISSN
2023 Impact Factor: 3.1
2023 SCImago Journal Rankings: 1.566
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorShao, Hengyi-
dc.contributor.authorZhu, Qingwei-
dc.contributor.authorLu, Huasong-
dc.contributor.authorChang, Amanda-
dc.contributor.authorGao, Carol-
dc.contributor.authorZhou, Qiang-
dc.contributor.authorLuo, Kunxin-
dc.date.accessioned2023-01-13T03:01:48Z-
dc.date.available2023-01-13T03:01:48Z-
dc.date.issued2020-
dc.identifier.citationMolecular Biology of the Cell, 2020, v. 31, n. 17, p. 1867-1878-
dc.identifier.issn1059-1524-
dc.identifier.urihttp://hdl.handle.net/10722/324142-
dc.description.abstractThe positive transcription elongation factor b (P-TEFb), composed of CDK9 and cyclin T, stimulates transcriptional elongation by RNA polymerase (Pol) II and regulates cell growth and differentiation. Recently, we demonstrated that P-TEFb also controls the expression of EMT regulators to promote breast cancer progression. In the nucleus, more than half of P-TEFb are sequestered in the inactive-state 7SK snRNP complex. Here, we show that the assembly of the 7SK snRNP is preceded by an intermediate complex between HEXIM1 and P-TEFb that allows transfer of the kinase active P-TEFb from Hsp90 to 7SK snRNP for its suppression. Down-regulation of HEXIM1 locks P-TEFb in the Hsp90 complex, keeping it in the active state to enhance breast cancer progression, but also rendering the cells highly sensitive to Hsp90 inhibition. Because HEXIM1 is often down-regulated in human triple-negative breast cancer (TNBC), these cells are particularly sensitive to Hsp90 inhibition. Our study provides a mechanistic explanation for the increased sensitivity of TNBC to Hsp90 inhibition.-
dc.languageeng-
dc.relation.ispartofMolecular Biology of the Cell-
dc.titleHEXIM1 controls P-TEFb processing and regulates drug sensitivity in triple-negative breast cancer-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1091/mbc.E19-12-0704-
dc.identifier.pmid32520633-
dc.identifier.scopuseid_2-s2.0-85089125314-
dc.identifier.volume31-
dc.identifier.issue17-
dc.identifier.spage1867-
dc.identifier.epage1878-
dc.identifier.eissn1939-4586-
dc.identifier.isiWOS:000556555700005-

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