PXD024191

PXD024191 is an original dataset announced via ProteomeXchange.

Title	Interaction with the CCT chaperonin complex limits cytotoxicity from the APOBEC3A cytosine deaminase.
Description	The APOBEC3 cytosine deaminases are implicated as the cause of a prevalent somatic mutation pattern found in cancer genomes. The APOBEC3 enzymes act as viral restriction factors by mutating viral genomes. Mutation of the cellular genome is presumed to be an off-target activity of the enzymes, although the regulatory measures for APOBEC3 expression and activity remain undefined. It is therefore difficult to predict the circumstances that enable APOBEC3 interaction with cellular DNA that leads to mutagenesis. The APOBEC3A (A3A) enzyme is the most potent deaminase of the family. Using proteomics, we evaluated protein interactors of A3A to identify potential regulators. We found that A3A interacts with the Chaperonin Containing TCP-1 (CCT) complex, a cellular machine that assists in protein folding and function. Importantly, depletion of CCT resulted in increased A3A-induced cytotoxicity. Evaluation of cancer genomes demonstrated an enrichment of A3A mutational signatures in cancers with silencing mutations in CCT subunit genes. Together, these data suggest that the CCT complex interacts with A3A, and that disruption of CCT function results in increased A3A mutational activity.
HostingRepository	PRIDE
AnnounceDate	2021-07-02
AnnouncementXML	Submission_2021-07-01_22:43:32.599.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD024191
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Katarzyna Kulej
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2021-02-15 23:58:24	ID requested
⏵ 1	2021-07-01 22:43:32	announced

Dataset with its publication pending

submitter keyword: APOBEC3A, CCT chaperonin, cytosine deaminase, protein interaction, mutational signatures

Benjamin A. Garcia
contact affiliation	Benjamin A. Garcia, Ph.D., FRSC John McCrea Dickson M.D. Presidential Professor Director of Quantitative Proteomics Penn Epigenetics Institute Department of Biochemistry and Biophysics Smilow Center for Translational Research Perelman School of Medicine University of Pennsylvania Room 9-124 (office) 3400 Civic Center Blvd Philadelphia, PA 19104 215-573-9423 (office)
contact email	bgarci@pennmedicine.upenn.edu
lab head
Katarzyna Kulej
contact affiliation	Children's Hospital of Philadelphia
contact email	kulej.katarzyna@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD024191
     1. Label: PRIDE project
     2. Name: Interaction with the CCT chaperonin complex limits cytotoxicity from the APOBEC3A cytosine deaminase.