PXD020073-2

PXD020073 is an original dataset announced via ProteomeXchange.

Title	Heterogeneous adaptation of cysteine reactivity to a covalent oncometabolite
Description	Metabolism and signaling intersect in the genetic cancer syndrome hereditary leiomyomatosis and renal cell carcinoma (HLRCC), a disease in which mutation of the TCA cycle enzyme fumarate hydratase (FH) causes hyperaccumulation of fumarate. This electrophilic oncometabolite can alter gene activity at the level of transcription, via reversible inhibition of epigenetic dioxygenases, as well as posttranslationally, via covalent modification of cysteine residues. To better understand how metabolites function as covalent signals, here we report a chemoproteomic analysis of a kidney-derived HLRCC cell line. Building on previous studies, we applied a general reactivity probe to compile a dataset of cysteine residues sensitive to rescue of cellular FH activity. This revealed a broad upregulation of cysteine reactivity upon FH rescue, caused by an approximately equal proportion of transcriptional and posttranslational regulation in the rescue cell line. Gene ontology analysis highlights new targets and pathways potentially modulated by FH mutation. Comparison of the new dataset to literature studies highlights considerable heterogeneity in the adaptive response of cysteine-containing proteins in different models of HLRCC. Our analysis provides a resource for understanding the proteomic adaptation to fumarate accumulation, and a foundation for future efforts to exploit this knowledge for cancer therapy.
HostingRepository	PRIDE
AnnounceDate	2021-05-07
AnnouncementXML	Submission_2021-05-06_22:20:30.548.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Daniel Bak
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2020-06-28 23:45:33	ID requested
1	2021-05-06 07:10:32	announced
⏵ 2	2021-05-06 22:20:32	announced	2021-05-07: Updated project metadata.
3	2024-10-22 05:21:47	announced	2024-10-22: Updated project metadata.

10.1074/JBC.AC120.014993;

Perez M, Bak DW, Bergholtz SE, Crooks DR, Arimilli BS, Yang Y, Weerapana E, Linehan WM, Meier JL, Heterogeneous adaptation of cysteine reactivity to a covalent oncometabolite. J Biol Chem, 295(39):13410-13418(2020) [pubmed]

submitter keyword: Human, Cysteine Reactivity, Kidney, HLRCC, UOK268

Eranthie Weerapana
contact affiliation	Chemistry Department, Boston College, USA
contact email	eranthie@bc.edu
lab head
Daniel Bak
contact affiliation	Boston College
contact email	bakd@bc.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD020073
     1. Label: PRIDE project
     2. Name: Heterogeneous adaptation of cysteine reactivity to a covalent oncometabolite