PXD021033

PXD021033 is an original dataset announced via ProteomeXchange.

Title	Nuclear Translocation of Glutaminase GLS2 in Human Cancer Cells Associates with Proliferation Arrest and Differentiation
Description	Glutaminase (GA) catalyzes the first step in mitochondrial glutaminolysis playing a key role in cancer metabolic reprogramming. Humans express two types of GA isoforms: GLS and GLS2. GLS isozymes have been consistently related to cell proliferation, but the role of GLS2 in cancer remains poorly understood. GLS2 is repressed in many tumor cells and a better understanding of its function in tumorigenesis may further the development of new therapeutic approaches. We analyzed GLS2 expression in HCC, GBM and neuroblastoma cells, as well as in monkey COS-7 cells. We studied GLS2 expression after induction of differentiation with phorbol ester (PMA) and transduction with the full-length cDNA of GLS2. In parallel, we investigated cell cycle progression and levels of p53, p21 and c-Myc proteins. Using the baculovirus system, human GLS2 protein was overexpressed, purified and analyzed for posttranslational modifications employing a proteomics LC-MS/MS platform. We have demonstrated a dual targeting of GLS2 in human cancer cells. Immunocytochemistry and subcellular fractionation gave consistent results demonstrating nuclear and mitochondrial locations, with the latter being predominant. Nuclear targeting was confirmed in cancer cells overexpressing c-Myc- and GFP-tagged GLS2 proteins. We assessed the subnuclear location finding a widespread distribution of GLS2 in the nucleoplasm without clear overlapping with specific nuclear substructures. GLS2 expression and nuclear accrual notably increased by treatment of SH-SY5Y cells with PMA and it correlated with cell cycle arrest at G2/M, upregulation of tumor suppressor p53 and p21 protein. A similar response was obtained by overexpression of GLS2 in T98G glioma cells, including downregulation of oncogene c-Myc. Furthermore, human GLS2 was identified as being hypusinated by MS analysis, a posttranslational modification which may be relevant for its nuclear targeting and/or function. Our studies provide evidence for a tumor suppressor role of GLS2 in certain types of cancer. The data imply that GLS2 can be regarded as a highly mobile and multilocalizing protein translocated to both mitochondria and nuclei. Upregulation of GLS2 in cancer cells induced an antiproliferative response with cell cycle arrest at the G2/M phase.
HostingRepository	PRIDE
AnnounceDate	2021-09-09
AnnouncementXML	Submission_2021-09-09_02:27:55.069.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Fernando J. Sialana
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2020-08-20 22:52:36	ID requested
⏵ 1	2021-09-09 02:27:56	announced

L, ó, pez de la Oliva AR, Campos-Sandoval JA, G, ó, mez-Garc, í, a MC, Cardona C, Mart, í, n-Rufi, á, n M, Sialana FJ, Castilla L, Bae N, Lobo C, Pe, ñ, alver A, Garc, í, a-Frutos M, Carro D, Enrique V, Paz JC, Mirmira RG, Guti, é, rrez A, Alonso FJ, Segura JA, Mat, é, s JM, Lubec G, M, á, rquez J, Nuclear Translocation of Glutaminase GLS2 in Human Cancer Cells Associates with Proliferation Arrest and Differentiation. Sci Rep, 10(1):2259(2020) [pubmed]

L, ó, pez de la Oliva AR, Campos-Sandoval JA, G, ó, mez-Garc, í, a MC, Cardona C, Mart, í, n-Rufi, á, n M, Sialana FJ, Castilla L, Bae N, Lobo C, Pe, ñ, alver A, Garc, í, a-Frutos M, Carro D, Enrique V, Paz JC, Mirmira RG, Guti, é, rrez A, Alonso FJ, Segura JA, Mat, é, s JM, Lubec G, M, á, rquez J, Author Correction: Nuclear Translocation of Glutaminase GLS2 in Human Cancer Cells Associates with Proliferation Arrest and Differentiation. Sci Rep, 11(1):249(2021) [pubmed]

submitter keyword: GLS2

Fernando Sialana
contact affiliation	Private Medical University of Salzburg
contact email	gert.lubec@lubeclab.com
lab head
Fernando J. Sialana
contact affiliation	Institute of Cancer Research
contact email	fsialana@yahoo.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD021033
     1. Label: PRIDE project
     2. Name: Nuclear Translocation of Glutaminase GLS2 in Human Cancer Cells Associates with Proliferation Arrest and Differentiation