PXD022128-1

PXD022128 is an original dataset announced via ProteomeXchange.

Title	A genome-wide screen for essentiality upon telomerase inhibition identifies a novel p53 regulator, C16ORF72/TAPR1
Description	Telomere 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.
HostingRepository	PRIDE
AnnounceDate	2021-03-04
AnnouncementXML	Submission_2021-03-04_11:03:28.233.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD022128
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Eric Bonneil
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-10-22 01:35:41	ID requested
⏵ 1	2021-03-04 11:03:28	announced

Dataset with its publication pending

submitter keyword: CRISPR-Cas9, genome-wide screen, telomere erosion, telomerase inhibitor, p53, C16ORF72

Lea Harrington
contact affiliation	IRIC-Université de Montréal
contact email	lea.harrington@umontreal.ca
lab head
Eric Bonneil
contact affiliation	Proteomic Platform
contact email	eric.bonneil@umontreal.ca
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD022128
     1. Label: PRIDE project
     2. Name: A genome-wide screen for essentiality upon telomerase inhibition identifies a novel p53 regulator, C16ORF72/TAPR1