PXD052836-2

PXD052836 is an original dataset announced via ProteomeXchange.

Title	FAM122A ensures cell cycle interphase progression and checkpoint control by inhibiting B55⍺/PP2A through helical motifs
Description	The 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
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:54:38.061.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xavier Graña
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-04 11:36:28	ID requested
1	2024-08-10 16:16:19	announced
⏵ 2	2024-10-22 06:54:41	announced	2024-10-22: Updated project metadata.

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;

submitter keyword: B55α,PP2A, FAM122A

Xavier Graña
contact affiliation	Temple University Lewis Katz School of Medicine, Philadelphia, Pennsylvania, United States
contact email	xgrana@temple.edu
lab head
Xavier Graña
contact affiliation	Temple University Lewis Katz School of Medicine
contact email	xgrana@temple.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD052836
     1. Label: PRIDE project
     2. Name: FAM122A ensures cell cycle interphase progression and checkpoint control by inhibiting B55⍺/PP2A through helical motifs