Role of Hsp70 in Cancer Growth and Survival

Marcus      P.D. Hatfield; Sandor      Lovas

doi:10.2174/092986612800493968

Abstract

Hsp70 is a highly conserved protein that refolds misfolded proteins and has numerous housekeeping functions which regulate apoptosis and other cell activities. Hsp70 consists of a nucleotide binding domain which binds ATP and a substrate binding domain that binds misfolded proteins. The substrate binding domain contains a peptide binding pocket which is covered by a helical lid. In humans, there are three major cytosolic Hsp70 isotypes, Hsp70-8, Hsp70-1 and Hsp70-2. Leukemic and numerous other cancer cells have a greater amount of Hsp70-1 and -2, which help the cancer cells inhibit apoptosis in response to stress. This review summarizes the structure and role of Hsp70 proteins in cancer survival.

Keywords: Heat shock protein, Hsp70, structure, cancer, inhibition, housekeeping functions, apoptosis, substrate binding domain, cancer cells, nucleotide-binding domain (NBD), DnaK, ATPase, ATP-induced high-to-low affinity, phospholipases