PXD024191 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2021-02-15 23:58:24 | ID requested | |
⏵ 1 | 2021-07-01 22:43:32 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: APOBEC3A, CCT chaperonin, cytosine deaminase, protein interaction, mutational signatures |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD024191
- Label: PRIDE project
- Name: Interaction with the CCT chaperonin complex limits cytotoxicity from the APOBEC3A cytosine deaminase.