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Article: PP2B and PP1α cooperatively disrupt 7SK snRNP to release P-TEFb for transcription in response to Ca2+ signaling

TitlePP2B and PP1α cooperatively disrupt 7SK snRNP to release P-TEFb for transcription in response to Ca<sup>2+</sup> signaling
Authors
KeywordsCa signal transduction 2+
CDK activation
P-TEFb
Protein phosphatases
Transcriptional elongation
Issue Date2008
Citation
Genes and Development, 2008, v. 22, n. 10, p. 1356-1368 How to Cite?
AbstractThe positive transcription elongation factor b (P-TEFb), consisting of Cdk9 and cyclin T, stimulates RNA polymerase II elongation and cotranscriptional pre-mRNA processing. To accommodate different growth conditions and transcriptional demands, a reservoir of P-TEFb is kept in an inactive state in the multisubunit 7SK snRNP. Under certain stress or disease conditions, P-TEFb is released to activate transcription, although the signaling pathway(s) that controls this is largely unknown. Here, through analyzing the UV- or hexamethylene bisacetamide (HMBA)-induced release of P-TEFb from 7SK snRNP, an essential role for the calcium ion (Ca2+)-calmodulin-protein phosphatase 2B (PP2B) signaling pathway is revealed. However, Ca2+ signaling alone is insufficient, and PP2B must act sequentially and cooperatively with protein phosphatase 1α (PP1α) to disrupt 7SK snRNP. Activated by UV/HMBA and facilitated by a PP2B-induced conformational change in 7SK snRNP, PP1α releases P-TEFb through dephosphorylating phospho-Thr186 in the Cdk9 T-loop. This event is also necessary for the subsequent recruitment of P-TEFb by the bromodomain protein Brd4 to the preinitiation complex, where Cdk9 remains unphosphorylated and inactive until after the synthesis of a short RNA. Thus, through cooperatively dephosphorylating Cdk9 in response to Ca2+ signaling, PP2B and PP1α alter the P-TEFb functional equilibrium through releasing P-TEFb from 7SK snRNP for transcription. © 2008 by Cold Spring Harbor Laboratory Press.
Persistent Identifierhttp://hdl.handle.net/10722/323819
ISSN
2023 Impact Factor: 7.5
2023 SCImago Journal Rankings: 5.015
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChen, Ruichuan-
dc.contributor.authorLiu, Min-
dc.contributor.authorLi, Huan-
dc.contributor.authorXue, Yuhua-
dc.contributor.authorRamey, Wanichaya N.-
dc.contributor.authorHe, Nanhai-
dc.contributor.authorAi, Nanping-
dc.contributor.authorLuo, Haohong-
dc.contributor.authorZhu, Ying-
dc.contributor.authorZhou, Nan-
dc.contributor.authorZhou, Qiang-
dc.date.accessioned2023-01-13T02:59:33Z-
dc.date.available2023-01-13T02:59:33Z-
dc.date.issued2008-
dc.identifier.citationGenes and Development, 2008, v. 22, n. 10, p. 1356-1368-
dc.identifier.issn0890-9369-
dc.identifier.urihttp://hdl.handle.net/10722/323819-
dc.description.abstractThe positive transcription elongation factor b (P-TEFb), consisting of Cdk9 and cyclin T, stimulates RNA polymerase II elongation and cotranscriptional pre-mRNA processing. To accommodate different growth conditions and transcriptional demands, a reservoir of P-TEFb is kept in an inactive state in the multisubunit 7SK snRNP. Under certain stress or disease conditions, P-TEFb is released to activate transcription, although the signaling pathway(s) that controls this is largely unknown. Here, through analyzing the UV- or hexamethylene bisacetamide (HMBA)-induced release of P-TEFb from 7SK snRNP, an essential role for the calcium ion (Ca2+)-calmodulin-protein phosphatase 2B (PP2B) signaling pathway is revealed. However, Ca2+ signaling alone is insufficient, and PP2B must act sequentially and cooperatively with protein phosphatase 1α (PP1α) to disrupt 7SK snRNP. Activated by UV/HMBA and facilitated by a PP2B-induced conformational change in 7SK snRNP, PP1α releases P-TEFb through dephosphorylating phospho-Thr186 in the Cdk9 T-loop. This event is also necessary for the subsequent recruitment of P-TEFb by the bromodomain protein Brd4 to the preinitiation complex, where Cdk9 remains unphosphorylated and inactive until after the synthesis of a short RNA. Thus, through cooperatively dephosphorylating Cdk9 in response to Ca2+ signaling, PP2B and PP1α alter the P-TEFb functional equilibrium through releasing P-TEFb from 7SK snRNP for transcription. © 2008 by Cold Spring Harbor Laboratory Press.-
dc.languageeng-
dc.relation.ispartofGenes and Development-
dc.subjectCa signal transduction 2+-
dc.subjectCDK activation-
dc.subjectP-TEFb-
dc.subjectProtein phosphatases-
dc.subjectTranscriptional elongation-
dc.titlePP2B and PP1α cooperatively disrupt 7SK snRNP to release P-TEFb for transcription in response to Ca<sup>2+</sup> signaling-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1101/gad.1636008-
dc.identifier.pmid18483222-
dc.identifier.scopuseid_2-s2.0-44149117974-
dc.identifier.volume22-
dc.identifier.issue10-
dc.identifier.spage1356-
dc.identifier.epage1368-
dc.identifier.eissn1549-5477-
dc.identifier.isiWOS:000255904500011-

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