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DEPDC1/LET-99 participates in an evolutionarily conserved pathway for anti-tubulin drug-induced apoptosis.

Publication ,  Journal Article
Sendoel, A; Maida, S; Zheng, X; Teo, Y; Stergiou, L; Rossi, C-A; Subasic, D; Pinto, SM; Kinchen, JM; Shi, M; Boettcher, S; Meyer, JN; Bano, D ...
Published in: Nature cell biology
August 2014

Microtubule-targeting chemotherapeutics induce apoptosis in cancer cells by promoting the phosphorylation and degradation of the anti-apoptotic BCL-2 family member MCL1. The signalling cascade linking microtubule disruption to MCL1 degradation remains however to be defined. Here, we establish an in vivo screening strategy in Caenorhabditis elegans to uncover genes involved in chemotherapy-induced apoptosis. Using an RNAi-based screen, we identify three genes required for vincristine-induced apoptosis. We show that the DEP domain protein LET-99 acts upstream of the heterotrimeric G protein alpha subunit GPA-11 to control activation of the stress kinase JNK-1. The human homologue of LET-99, DEPDC1, similarly regulates vincristine-induced cell death by promoting JNK-dependent degradation of the BCL-2 family protein MCL1. Collectively, these data uncover an evolutionarily conserved mediator of anti-tubulin drug-induced apoptosis and suggest that DEPDC1 levels could be an additional determinant for therapy response upstream of MCL1.

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Published In

Nature cell biology

DOI

EISSN

1476-4679

ISSN

1465-7392

Publication Date

August 2014

Volume

16

Issue

8

Start / End Page

812 / 820

Related Subject Headings

  • Vincristine
  • Tubulin Modulators
  • Signal Transduction
  • Repressor Proteins
  • RNA Interference
  • Proteolysis
  • Phosphorylation
  • Neoplasm Proteins
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Mutation
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Sendoel, A., Maida, S., Zheng, X., Teo, Y., Stergiou, L., Rossi, C.-A., … Hengartner, M. O. (2014). DEPDC1/LET-99 participates in an evolutionarily conserved pathway for anti-tubulin drug-induced apoptosis. Nature Cell Biology, 16(8), 812–820. https://doi.org/10.1038/ncb3010
Sendoel, Ataman, Simona Maida, Xue Zheng, Youjin Teo, Lilli Stergiou, Carlo-Alberto Rossi, Deni Subasic, et al. “DEPDC1/LET-99 participates in an evolutionarily conserved pathway for anti-tubulin drug-induced apoptosis.Nature Cell Biology 16, no. 8 (August 2014): 812–20. https://doi.org/10.1038/ncb3010.
Sendoel A, Maida S, Zheng X, Teo Y, Stergiou L, Rossi C-A, et al. DEPDC1/LET-99 participates in an evolutionarily conserved pathway for anti-tubulin drug-induced apoptosis. Nature cell biology. 2014 Aug;16(8):812–20.
Sendoel, Ataman, et al. “DEPDC1/LET-99 participates in an evolutionarily conserved pathway for anti-tubulin drug-induced apoptosis.Nature Cell Biology, vol. 16, no. 8, Aug. 2014, pp. 812–20. Epmc, doi:10.1038/ncb3010.
Sendoel A, Maida S, Zheng X, Teo Y, Stergiou L, Rossi C-A, Subasic D, Pinto SM, Kinchen JM, Shi M, Boettcher S, Meyer JN, Manz MG, Bano D, Hengartner MO. DEPDC1/LET-99 participates in an evolutionarily conserved pathway for anti-tubulin drug-induced apoptosis. Nature cell biology. 2014 Aug;16(8):812–820.

Published In

Nature cell biology

DOI

EISSN

1476-4679

ISSN

1465-7392

Publication Date

August 2014

Volume

16

Issue

8

Start / End Page

812 / 820

Related Subject Headings

  • Vincristine
  • Tubulin Modulators
  • Signal Transduction
  • Repressor Proteins
  • RNA Interference
  • Proteolysis
  • Phosphorylation
  • Neoplasm Proteins
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Mutation