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PXD053627

PXD053627 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleIntegrative Proteomics Identifies MePCE as a Substrate of CDK9 for Releasing P-TEFb from 7SK snRNP Under Genotoxic Stress
DescriptionThe dynamic phosphorylation process regulated by the positive transcription elongation factor b (P-TEFb), a CDK9-cyclin T heterodimer, is critical for transcription elongation of numerous mammalian genes. Most P-TEFb in cells are normally sequestered in the 7SK snRNP, and their release from this complex is well-controlled to maintain proper cell homeostasis and growth. The comprehensive profiling of CDK9 substrates is essential for understanding diverse functions of P-TEFb in controlling gene expression. Here, integrative proteomics methodologies are developed to globally identify the potential substrates of CDK9 in vivo. Our results show that the 7SK methylphosphate capping enzyme MePCE is directly phosphorylated by CDK9 within the 7SK snRNP, which is known to exhibit little kinase activity toward other known CDK9 substrates. Upon ultraviolet radiation, MePCE becomes phosphorylated, leading to the dissociation of 7SK snRNP and release of P-TEFb to activate transcription. Meanwhile, the phosphorylation of MePCE does not affect its methyltransferase activity toward 7SK RNA. Our data suggest that even though CDK9 in 7SK snRNP has little kinase activity toward external substrates, it can phosphorylate the snRNP integral component MePCE, which is required to release P-TEFb. This novel inside-to-outside mode of P-TEFb activation may serve as a critical checkpoint in regulating gene transcription under stressful conditions.
HostingRepositoryiProX
AnnounceDate2024-07-03
AnnouncementXMLSubmission_2024-09-29_19:52:33.139.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterChunjing Chen
SpeciesList scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationListphosphorylated residue; (13)C labeled residue
InstrumentOrbitrap Fusion; Q Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-07-03 20:43:55ID requested
12024-09-29 19:52:33announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Phosphorylation
Phosphoproteomics
MePCE
CDK9 substrates
P-TEFb
Contact List
Xiang Gao
contact affiliationXiamen University
contact emailxgao@xmu.edu.cn
lab head
Chunjing Chen
contact affiliationXiamen University
contact emailchencj_1106@163.com
dataset submitter
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iProX dataset URI