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PXD022128-1

PXD022128 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleA genome-wide screen for essentiality upon telomerase inhibition identifies a novel p53 regulator, C16ORF72/TAPR1
DescriptionTelomere erosion contributes to age-associated tissue dysfunction and senescence, and p53 plays a crucial role in this response. We undertook a genome-wide screen to identify gene deletions that sensitized p53-positive human cells to loss of telomere integrity, and uncovered a previously unannotated gene, C16ORF72, which we term Telomere Attrition and p53 Response 1: TAPR1. CRISPR-Cas9 mediated deletion of TAPR1 led to elevated p53 and induction of p53 transcriptional targets. TAPR1-disrupted cells exhibited a synthetic-sick relationship with the loss of telomerase, or treatment with the topoisomerase II inhibitor doxorubicin. Stabilization of p53 with nutlin-3a further decreased cell fitness in cells lacking TAPR1 or telomerase, whereas deletion of TP53 rescued the decreased fitness of TAPR1-deleted cells. We propose that TAPR1 regulates p53 turnover, thereby tapering the p53-dependent response to telomere erosion. We discuss the possible implications of such a mechanism in the preservation of genome integrity during senescence or aging.
HostingRepositoryPRIDE
AnnounceDate2021-03-04
AnnouncementXMLSubmission_2021-03-04_11:03:28.233.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD022128
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterEric Bonneil
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-10-22 01:35:41ID requested
12021-03-04 11:03:28announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: CRISPR-Cas9, genome-wide screen, telomere erosion, telomerase inhibitor, p53, C16ORF72
Contact List
Lea Harrington
contact affiliationIRIC-Université de Montréal
contact emaillea.harrington@umontreal.ca
lab head
Eric Bonneil
contact affiliationProteomic Platform
contact emaileric.bonneil@umontreal.ca
dataset submitter
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Dataset FTP location
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