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PXD052836-1

PXD052836 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleFAM122A ensures cell cycle interphase progression and checkpoint control by inhibiting B55⍺/PP2A through helical motifs
DescriptionThe Ser/Thr protein phosphatase 2A (PP2A) regulates the dephosphorylation of many phosphoproteins. Substrate recognition are mediated by B regulatory subunits. Here, we report the identification of a substrate conserved motif [RK]-V-x-x-[VI]-R in FAM122A, an inhibitor of B55α/PP2A. This motif is necessary for FAM122A binding to B55α, and computational structure prediction suggests the motif, which is helical, blocks substrate docking to the same site. In this model, FAM122A also spatially constrains substrate access by occluding the catalytic subunit. Consistently, FAM122A functions as a competitive inhibitor as it prevents substrate binding and dephosphorylation of CDK substrates by B55α/PP2A in cell lysates. FAM122A deficiency in human cell lines reduces the proliferation rate, cell cycle progression, and hinders G1/S and intra-S phase cell cycle checkpoints. FAM122A-KO in HEK293 cells attenuates CHK1 and CHK2 activation in response to replication stress. Overall, these data strongly suggest that FAM122A is a short helical motif (SHeM)-dependent, substrate-competitive inhibitor of B55α/PP2A that suppresses multiple functions of B55α in the DNA damage response and in timely progression through the cell cycle interphase
HostingRepositoryPRIDE
AnnounceDate2024-08-11
AnnouncementXMLSubmission_2024-08-10_16:16:18.490.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterXavier Graña
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-06-04 11:36:28ID requested
12024-08-10 16:16:19announced
22024-10-22 06:54:41announced2024-10-22: Updated project metadata.
Publication List
Wasserman JS, Faezov B, Patel KR, Kurimchak AM, Palacio SM, Glass DJ, Fowle H, McEwan BC, Xu Q, Zhao Z, Cressey L, Johnson N, Duncan JS, Kettenbach AN, Dunbrack RL, Gra, ñ, a X, /PP2A through helical motifs. Nat Commun, 15(1):5776(2024) [pubmed]
10.1038/s41467-024-50015-7;
Keyword List
submitter keyword: B55α,PP2A, FAM122A
Contact List
Xavier Graña
contact affiliationTemple University Lewis Katz School of Medicine, Philadelphia, Pennsylvania, United States
contact emailxgrana@temple.edu
lab head
Xavier Graña
contact affiliationTemple University Lewis Katz School of Medicine
contact emailxgrana@temple.edu
dataset submitter
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Dataset FTP location
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