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Small ubiquitin-like modifier 1-3 conjugation [corrected] is activated in human astrocytic brain tumors and is required for glioblastoma cell survival.

Publication ,  Journal Article
Yang, W; Wang, L; Roehn, G; Pearlstein, RD; Ali-Osman, F; Pan, H; Goldbrunner, R; Krantz, M; Harms, C; Paschen, W
Published in: Cancer Sci
January 2013

Small ubiquitin-like modifier (SUMO1-3) constitutes a group of proteins that conjugate to lysine residues of target proteins thereby modifying their activity, stability, and subcellular localization. A large number of SUMO target proteins are transcription factors and other nuclear proteins involved in gene expression. Furthermore, SUMO conjugation plays key roles in genome stability, quality control of newly synthesized proteins, proteasomal degradation of proteins, and DNA damage repair. Any marked increase in levels of SUMO-conjugated proteins is therefore expected to have a major impact on the fate of cells. We show here that SUMO conjugation is activated in human astrocytic brain tumors. Levels of both SUMO1- and SUMO2/3-conjugated proteins were markedly increased in tumor samples. The effect was least pronounced in low-grade astrocytoma (WHO Grade II) and most pronounced in glioblastoma multiforme (WHO Grade IV). We also found a marked rise in levels of Ubc9, the only SUMO conjugation enzyme identified so far. Blocking SUMO1-3 conjugation in glioblastoma cells by silencing their expression blocked DNA synthesis, cell growth, and clonogenic survival of cells. It also resulted in DNA-dependent protein kinase-induced phosphorylation of H2AX, indicative of DNA double-strand damage, and G(2) /M cell cycle arrest. Collectively, these findings highlight the pivotal role of SUMO conjugation in DNA damage repair processes and imply that the SUMO conjugation pathway could be a new target of therapeutic intervention aimed at increasing the sensitivity of glioblastomas to radiotherapy and chemotherapy.

Duke Scholars

Published In

Cancer Sci

DOI

EISSN

1349-7006

Publication Date

January 2013

Volume

104

Issue

1

Start / End Page

70 / 77

Location

England

Related Subject Headings

  • Ubiquitins
  • Ubiquitin-Conjugating Enzymes
  • Tumor Cells, Cultured
  • Sumoylation
  • Small Ubiquitin-Related Modifier Proteins
  • SUMO-1 Protein
  • RNA Interference
  • Phosphorylation
  • Oncology & Carcinogenesis
  • MicroRNAs
 

Citation

APA
Chicago
ICMJE
MLA
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Yang, W., Wang, L., Roehn, G., Pearlstein, R. D., Ali-Osman, F., Pan, H., … Paschen, W. (2013). Small ubiquitin-like modifier 1-3 conjugation [corrected] is activated in human astrocytic brain tumors and is required for glioblastoma cell survival. Cancer Sci, 104(1), 70–77. https://doi.org/10.1111/cas.12047
Yang, Wei, Liangli Wang, Gabriele Roehn, Robert D. Pearlstein, Francis Ali-Osman, Hongjie Pan, Roland Goldbrunner, Matthew Krantz, Christoph Harms, and Wulf Paschen. “Small ubiquitin-like modifier 1-3 conjugation [corrected] is activated in human astrocytic brain tumors and is required for glioblastoma cell survival.Cancer Sci 104, no. 1 (January 2013): 70–77. https://doi.org/10.1111/cas.12047.
Yang W, Wang L, Roehn G, Pearlstein RD, Ali-Osman F, Pan H, et al. Small ubiquitin-like modifier 1-3 conjugation [corrected] is activated in human astrocytic brain tumors and is required for glioblastoma cell survival. Cancer Sci. 2013 Jan;104(1):70–7.
Yang, Wei, et al. “Small ubiquitin-like modifier 1-3 conjugation [corrected] is activated in human astrocytic brain tumors and is required for glioblastoma cell survival.Cancer Sci, vol. 104, no. 1, Jan. 2013, pp. 70–77. Pubmed, doi:10.1111/cas.12047.
Yang W, Wang L, Roehn G, Pearlstein RD, Ali-Osman F, Pan H, Goldbrunner R, Krantz M, Harms C, Paschen W. Small ubiquitin-like modifier 1-3 conjugation [corrected] is activated in human astrocytic brain tumors and is required for glioblastoma cell survival. Cancer Sci. 2013 Jan;104(1):70–77.
Journal cover image

Published In

Cancer Sci

DOI

EISSN

1349-7006

Publication Date

January 2013

Volume

104

Issue

1

Start / End Page

70 / 77

Location

England

Related Subject Headings

  • Ubiquitins
  • Ubiquitin-Conjugating Enzymes
  • Tumor Cells, Cultured
  • Sumoylation
  • Small Ubiquitin-Related Modifier Proteins
  • SUMO-1 Protein
  • RNA Interference
  • Phosphorylation
  • Oncology & Carcinogenesis
  • MicroRNAs