PXD022128 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-10-22 01:35:41 | ID requested | |
⏵ 1 | 2021-03-04 11:03:28 | announced | |
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 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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
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- PRIDE
- PXD022128
- Label: PRIDE project
- Name: A genome-wide screen for essentiality upon telomerase inhibition identifies a novel p53 regulator, C16ORF72/TAPR1