---
_id: '7487'
abstract:
- lang: eng
  text: '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.'
article_number: '2259'
article_processing_charge: No
article_type: original
author:
- first_name: Amada R.
  full_name: López De La Oliva, Amada R.
  last_name: López De La Oliva
- first_name: José A.
  full_name: Campos-Sandoval, José A.
  last_name: Campos-Sandoval
- first_name: María C.
  full_name: Gómez-García, María C.
  last_name: Gómez-García
- first_name: Carolina
  full_name: Cardona, Carolina
  last_name: Cardona
- first_name: Mercedes
  full_name: Martín-Rufián, Mercedes
  last_name: Martín-Rufián
- first_name: Fernando J.
  full_name: Sialana, Fernando J.
  last_name: Sialana
- first_name: Laura
  full_name: Castilla, Laura
  last_name: Castilla
- first_name: Narkhyun
  full_name: Bae, Narkhyun
  id: 3A5F7CD8-F248-11E8-B48F-1D18A9856A87
  last_name: Bae
- first_name: Carolina
  full_name: Lobo, Carolina
  last_name: Lobo
- first_name: Ana
  full_name: Peñalver, Ana
  last_name: Peñalver
- first_name: Marina
  full_name: García-Frutos, Marina
  last_name: García-Frutos
- first_name: David
  full_name: Carro, David
  last_name: Carro
- first_name: Victoria
  full_name: Enrique, Victoria
  last_name: Enrique
- first_name: José C.
  full_name: Paz, José C.
  last_name: Paz
- first_name: Raghavendra G.
  full_name: Mirmira, Raghavendra G.
  last_name: Mirmira
- first_name: Antonia
  full_name: Gutiérrez, Antonia
  last_name: Gutiérrez
- first_name: Francisco J.
  full_name: Alonso, Francisco J.
  last_name: Alonso
- first_name: Juan A.
  full_name: Segura, Juan A.
  last_name: Segura
- first_name: José M.
  full_name: Matés, José M.
  last_name: Matés
- first_name: Gert
  full_name: Lubec, Gert
  last_name: Lubec
- first_name: Javier
  full_name: Márquez, Javier
  last_name: Márquez
citation:
  ama: López De La Oliva AR, Campos-Sandoval JA, Gómez-García MC, et al. Nuclear translocation
    of glutaminase GLS2 in human cancer cells associates with proliferation arrest
    and differentiation. <i>Scientific reports</i>. 2020;10(1). doi:<a href="https://doi.org/10.1038/s41598-020-58264-4">10.1038/s41598-020-58264-4</a>
  apa: López De La Oliva, A. R., Campos-Sandoval, J. A., Gómez-García, M. C., Cardona,
    C., Martín-Rufián, M., Sialana, F. J., … Márquez, J. (2020). Nuclear translocation
    of glutaminase GLS2 in human cancer cells associates with proliferation arrest
    and differentiation. <i>Scientific Reports</i>. Springer Nature. <a href="https://doi.org/10.1038/s41598-020-58264-4">https://doi.org/10.1038/s41598-020-58264-4</a>
  chicago: López De La Oliva, Amada R., José A. Campos-Sandoval, María C. Gómez-García,
    Carolina Cardona, Mercedes Martín-Rufián, Fernando J. Sialana, Laura Castilla,
    et al. “Nuclear Translocation of Glutaminase GLS2 in Human Cancer Cells Associates
    with Proliferation Arrest and Differentiation.” <i>Scientific Reports</i>. Springer
    Nature, 2020. <a href="https://doi.org/10.1038/s41598-020-58264-4">https://doi.org/10.1038/s41598-020-58264-4</a>.
  ieee: A. R. López De La Oliva <i>et al.</i>, “Nuclear translocation of glutaminase
    GLS2 in human cancer cells associates with proliferation arrest and differentiation,”
    <i>Scientific reports</i>, vol. 10, no. 1. Springer Nature, 2020.
  ista: López De La Oliva AR, Campos-Sandoval JA, Gómez-García MC, Cardona C, Martín-Rufián
    M, Sialana FJ, Castilla L, Bae N, Lobo C, Peñalver A, García-Frutos M, Carro D,
    Enrique V, Paz JC, Mirmira RG, Gutiérrez A, Alonso FJ, Segura JA, Matés JM, Lubec
    G, Márquez J. 2020. Nuclear translocation of glutaminase GLS2 in human cancer
    cells associates with proliferation arrest and differentiation. Scientific reports.
    10(1), 2259.
  mla: López De La Oliva, Amada R., et al. “Nuclear Translocation of Glutaminase GLS2
    in Human Cancer Cells Associates with Proliferation Arrest and Differentiation.”
    <i>Scientific Reports</i>, vol. 10, no. 1, 2259, Springer Nature, 2020, doi:<a
    href="https://doi.org/10.1038/s41598-020-58264-4">10.1038/s41598-020-58264-4</a>.
  short: A.R. López De La Oliva, J.A. Campos-Sandoval, M.C. Gómez-García, C. Cardona,
    M. Martín-Rufián, F.J. Sialana, L. Castilla, N. Bae, C. Lobo, A. Peñalver, M.
    García-Frutos, D. Carro, V. Enrique, J.C. Paz, R.G. Mirmira, A. Gutiérrez, F.J.
    Alonso, J.A. Segura, J.M. Matés, G. Lubec, J. Márquez, Scientific Reports 10 (2020).
date_created: 2020-02-16T23:00:49Z
date_published: 2020-02-10T00:00:00Z
date_updated: 2023-08-18T06:35:13Z
day: '10'
ddc:
- '570'
department:
- _id: CaBe
doi: 10.1038/s41598-020-58264-4
external_id:
  isi:
  - '000560694800012'
  pmid:
  - '32042057'
file:
- access_level: open_access
  checksum: c780bd87476a9c9e12668ff66de3dc96
  content_type: application/pdf
  creator: dernst
  date_created: 2020-02-18T07:43:21Z
  date_updated: 2020-07-14T12:47:59Z
  file_id: '7495'
  file_name: 2020_ScientificReport_Lopez.pdf
  file_size: 4703751
  relation: main_file
file_date_updated: 2020-07-14T12:47:59Z
has_accepted_license: '1'
intvolume: '        10'
isi: 1
issue: '1'
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
pmid: 1
publication: Scientific reports
publication_identifier:
  eissn:
  - '20452322'
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  link:
  - relation: erratum
    url: https://doi.org/10.1038/s41598-020-80651-0
scopus_import: '1'
status: public
title: Nuclear translocation of glutaminase GLS2 in human cancer cells associates
  with proliferation arrest and differentiation
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 10
year: '2020'
...