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

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

来源：ACS Chemical Biology, 2014, 9(8): 1698-1705.

DOI：10.1021/cb500256u

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.

• 出版日期2014-8