Hsc70 contributes to cancer cell survival by preventing Rab1A degradation under stress conditions

Masako Tanaka, Saya Mun, Akihito Harada, Yasuyuki Ohkawa, Azusa Inagaki, Soichi Sano, Katsuyuki Takahashi, Yasukatsu Izumi, Mayuko Osada-Oka, Hideki Wanibuchi, Masayo Yamagata, Tokihito Yukimura, Katsuyuki Miura, Masayuki Shiota, Hiroshi Iwao

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19 Citations (Scopus)

Abstract

Heat shock cognate protein 70 (Hsc70) acts as a molecular chaperone for the maintenance of intracellular proteins, which allows cancer cells to survive under proteotoxic stress. We attempted to use Hsc70 to identify key molecules in cancer cell survival. Here, we performed mass-spectrometry-based proteomics analysis utilizing affinity purification with anti-Hsc70 antibodies; as a result, 83 differentially expressed proteins were identified under stress conditions. This result implies that there was a change in the proteins with which Hsc70 interacted in response to stress. Among the proteins identified under both serum-depleted and 5-fluorouracil-treated conditions, Rab1A was identified as an essential molecule for cancer cell survival. Hsc70 interacted with Rab1A in a chaperone-dependent manner. In addition, Hsc70 knockdown decreased the level of Rab1A and increased the level of its ubiquitination under stress conditions, suggesting that Hsc70 prevented the degradation of Rab1A denatured by stress exposure. We also found that Rab1A knockdown induced cell death by inhibition of autophagosome formation. Rab1A may therefore contribute to overcoming proteotoxic insults, which allows cancer cells to survive under stress conditions. Analysis of Hsc70 interactors provided insight into changes of intracellular status. We expect further study of the Hsc70 interactome to provide a more comprehensive understanding of cancer cell physiology.

Original languageEnglish
Article numbere96785
JournalPloS one
Volume9
Issue number5
DOIs
Publication statusPublished - 2014 May 6

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Tanaka, M., Mun, S., Harada, A., Ohkawa, Y., Inagaki, A., Sano, S., Takahashi, K., Izumi, Y., Osada-Oka, M., Wanibuchi, H., Yamagata, M., Yukimura, T., Miura, K., Shiota, M., & Iwao, H. (2014). Hsc70 contributes to cancer cell survival by preventing Rab1A degradation under stress conditions. PloS one, 9(5), [e96785]. https://doi.org/10.1371/journal.pone.0096785