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Distinctive effects of the cellular inhibitor of apoptosis protein c-IAP2 through stabilization by XIAP in glioblastoma multiforme cells.

Publication ,  Journal Article
Yang, W; Cooke, M; Duckett, CS; Yang, X; Dorsey, JF
Published in: Cell Cycle
2014

Inhibitor of apoptosis proteins (IAPs) are extensively involved in NFκB signaling pathways. Regulation of c-IAP2 turnover by other proteins was investigated in glioblastoma multiforme (GBM) cells in the present study. When overexpressed, X-linked IAP (XIAP) enhanced expression of ectopic c-IAP2, but not c-IAP1, and endogenous c-IAP2 levels were reduced once XIAP expression was silenced. TNFα stimulation substantially increased c-IAP2 expression, and this upregulation was impaired by suppression of XIAP. Similarly, when XIAP was limiting due to severe hypoxic conditions, c-IAP2 levels were downregulated. These data together indicate that XIAP is an important regulator responsible for stabilization of c-IAP2 levels under different conditions. Protein interactions occur through binding of BIR2 and BIR3 domains of c-IAP2 with the RING finger of XIAP. XIAP inhibition of c-IAP2 auto-degradation was dependent on this physical interaction, and it was independent of XIAP E3 ligase activity. Global c-IAP2 ubiquitination was not affected by XIAP, although c-IAP2 levels were significantly increased. A CARD-RING-containing fragment of c-IAP2 was found to target XIAP for proteasome-independent degradation, but it was unable to sensitize GBM cells to chemo-reagents. The XIAP-stabilized c-IAP2 was found to enhance IκB-α phosphorylation on serines 32 and 36, and to antagonize XIAP-induced increase in mature Smac and Bcl10. Taken together, our data identify a distinctive role of c-IAP2 as stabilizer of XIAP, which is likely involved in regulation of NFκB activation and apoptosis in GBM cells.

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Published In

Cell Cycle

DOI

EISSN

1551-4005

Publication Date

2014

Volume

13

Issue

6

Start / End Page

992 / 1005

Location

United States

Related Subject Headings

  • X-Linked Inhibitor of Apoptosis Protein
  • Ubiquitination
  • Tumor Necrosis Factor-alpha
  • RING Finger Domains
  • NF-kappa B
  • Inhibitor of Apoptosis Proteins
  • Humans
  • Glioblastoma
  • Developmental Biology
  • Cell Line, Tumor
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Yang, W., Cooke, M., Duckett, C. S., Yang, X., & Dorsey, J. F. (2014). Distinctive effects of the cellular inhibitor of apoptosis protein c-IAP2 through stabilization by XIAP in glioblastoma multiforme cells. Cell Cycle, 13(6), 992–1005. https://doi.org/10.4161/cc.27880
Yang, Wensheng, Mariana Cooke, Colin S. Duckett, Xiaolu Yang, and Jay F. Dorsey. “Distinctive effects of the cellular inhibitor of apoptosis protein c-IAP2 through stabilization by XIAP in glioblastoma multiforme cells.Cell Cycle 13, no. 6 (2014): 992–1005. https://doi.org/10.4161/cc.27880.
Yang, Wensheng, et al. “Distinctive effects of the cellular inhibitor of apoptosis protein c-IAP2 through stabilization by XIAP in glioblastoma multiforme cells.Cell Cycle, vol. 13, no. 6, 2014, pp. 992–1005. Pubmed, doi:10.4161/cc.27880.

Published In

Cell Cycle

DOI

EISSN

1551-4005

Publication Date

2014

Volume

13

Issue

6

Start / End Page

992 / 1005

Location

United States

Related Subject Headings

  • X-Linked Inhibitor of Apoptosis Protein
  • Ubiquitination
  • Tumor Necrosis Factor-alpha
  • RING Finger Domains
  • NF-kappa B
  • Inhibitor of Apoptosis Proteins
  • Humans
  • Glioblastoma
  • Developmental Biology
  • Cell Line, Tumor