Affinity Purification Probes of Potential Use To Investigate the Endogenous Hsp70 Interactome in Cancer

نویسندگان

  • Anna Rodina
  • Tony Taldone
  • Yanlong Kang
  • Pallav D. Patel
  • John Koren
  • Pengrong Yan
  • Erica M. DaGama Gomes
  • Chenghua Yang
  • Maulik R. Patel
  • Liza Shrestha
  • Stefan O. Ochiana
  • Cristina Santarossa
  • Ronnie Maharaj
  • Alexander Gozman
  • Marc B. Cox
  • Hediye Erdjument-Bromage
  • Ronald C. Hendrickson
  • Leandro Cerchietti
  • Ari Melnick
  • Monica L. Guzman
  • Gabriela Chiosis
چکیده

Heat shock protein 70 (Hsp70) is a family of proteins with key roles in regulating malignancy. Cancer cells rely on Hsp70 to inhibit apoptosis, regulate senescence and autophagy, and maintain the stability of numerous onco-proteins. Despite these important biological functions in cancer, robust chemical tools that enable the analysis of the Hsp70-regulated proteome in a tumor-by-tumor manner are yet unavailable. Here we take advantage of a recently reported Hsp70 ligand to design and develop an affinity purification chemical toolset for potential use in the investigation of the endogenous Hsp70-interacting proteome in cancer. We demonstrate that these tools lock Hsp70 in complex with onco-client proteins and effectively isolate Hsp70 complexes for identification through biochemical techniques. Using these tools we provide proof-of-concept analyses that glimpse into the complex roles played by Hsp70 in maintaining a multitude of cell-specific malignancy-driving proteins.

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عنوان ژورنال:

دوره 9  شماره 

صفحات  -

تاریخ انتشار 2014