Skip to main content
construction release_alert
Scholars@Duke will be undergoing maintenance April 11-15. Some features may be unavailable during this time.
cancel

The small heat shock protein alpha B-crystallin is a novel inhibitor of TRAIL-induced apoptosis that suppresses the activation of caspase-3.

Publication ,  Journal Article
Kamradt, MC; Lu, M; Werner, ME; Kwan, T; Chen, F; Strohecker, A; Oshita, S; Wilkinson, JC; Yu, C; Oliver, PG; Duckett, CS; Buchsbaum, DJ ...
Published in: J Biol Chem
March 25, 2005

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor alpha family of cytokines that preferentially induces apoptosis in transformed cells, making it a promising cancer therapy. However, many neoplasms are resistant to TRAIL-induced apoptosis by mechanisms that are poorly understood. We demonstrate that the expression of the small heat shock protein alpha B-crystallin (but not other heat shock proteins or apoptosis-regulating proteins) correlates with TRAIL resistance in a panel of human cancer cell lines. Stable expression of wild-type alpha B-crystallin, but not a pseudophosphorylation mutant impaired in its assembly and chaperone function, protects cancer cells from TRAIL-induced caspase-3 activation and apoptosis in vitro. Furthermore, selective inhibition of alpha B-crystallin expression by RNA interference sensitizes cancer cells to TRAIL. In addition, wild-type alpha B-crystallin promotes xenograft tumor growth and inhibits TRAIL-induced apoptosis in vivo in nude mice, whereas a pseudophosphorylation alpha B-crystallin mutant impaired in its anti-apoptotic function inhibits xenograft tumor growth. Collectively, these findings indicate that alpha B-crystallin is a novel regulator of TRAIL-induced apoptosis and tumor growth. Moreover, these results demonstrate that targeted inhibition of alpha B-crystallin promotes TRAIL-induced apoptosis, thereby suggesting a novel strategy to overcome TRAIL resistance in cancer.

Duke Scholars

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

March 25, 2005

Volume

280

Issue

12

Start / End Page

11059 / 11066

Location

United States

Related Subject Headings

  • alpha-Crystallin B Chain
  • Tumor Necrosis Factor-alpha
  • TNF-Related Apoptosis-Inducing Ligand
  • RNA Interference
  • Membrane Glycoproteins
  • Humans
  • Female
  • Enzyme Activation
  • Cell Line, Tumor
  • Caspase Inhibitors
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kamradt, M. C., Lu, M., Werner, M. E., Kwan, T., Chen, F., Strohecker, A., … Cryns, V. L. (2005). The small heat shock protein alpha B-crystallin is a novel inhibitor of TRAIL-induced apoptosis that suppresses the activation of caspase-3. J Biol Chem, 280(12), 11059–11066. https://doi.org/10.1074/jbc.M413382200
Kamradt, Merideth C., Meiling Lu, Michael E. Werner, Toni Kwan, Feng Chen, Anne Strohecker, Shayna Oshita, et al. “The small heat shock protein alpha B-crystallin is a novel inhibitor of TRAIL-induced apoptosis that suppresses the activation of caspase-3.J Biol Chem 280, no. 12 (March 25, 2005): 11059–66. https://doi.org/10.1074/jbc.M413382200.
Kamradt MC, Lu M, Werner ME, Kwan T, Chen F, Strohecker A, et al. The small heat shock protein alpha B-crystallin is a novel inhibitor of TRAIL-induced apoptosis that suppresses the activation of caspase-3. J Biol Chem. 2005 Mar 25;280(12):11059–66.
Kamradt, Merideth C., et al. “The small heat shock protein alpha B-crystallin is a novel inhibitor of TRAIL-induced apoptosis that suppresses the activation of caspase-3.J Biol Chem, vol. 280, no. 12, Mar. 2005, pp. 11059–66. Pubmed, doi:10.1074/jbc.M413382200.
Kamradt MC, Lu M, Werner ME, Kwan T, Chen F, Strohecker A, Oshita S, Wilkinson JC, Yu C, Oliver PG, Duckett CS, Buchsbaum DJ, LoBuglio AF, Jordan VC, Cryns VL. The small heat shock protein alpha B-crystallin is a novel inhibitor of TRAIL-induced apoptosis that suppresses the activation of caspase-3. J Biol Chem. 2005 Mar 25;280(12):11059–11066.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

March 25, 2005

Volume

280

Issue

12

Start / End Page

11059 / 11066

Location

United States

Related Subject Headings

  • alpha-Crystallin B Chain
  • Tumor Necrosis Factor-alpha
  • TNF-Related Apoptosis-Inducing Ligand
  • RNA Interference
  • Membrane Glycoproteins
  • Humans
  • Female
  • Enzyme Activation
  • Cell Line, Tumor
  • Caspase Inhibitors