The carboxy-terminus of Hsp70-interacting protein (CHIP) is a ubiquitin ligase and co-chaperone belonging to Ubox family that plays a crucial role in the maintenance of cellular homeostasis by switching the equilibrium of the folding-refolding mechanism towards the proteasomal or lysosomal degradation pathway. It links molecular chaperones

viz

. HSC70

HSP70 and HSP90 with ubiquitin proteasome system (UPS)

acting as a quality control system. CHIP contains charged domain in between N-terminal tetratricopeptide repeat (TPR) and C-terminal Ubox domain. TPR domain interacts with the aberrant client proteins

via

chaperones while Ubox domain facilitates the ubiquitin transfer to the client proteins for ubiquitination. Thus

CHIP is a classic molecule that executes ubiquitination for degradation of client proteins. Further

CHIP has been found to be indulged in cellular differentiation

proliferation

metastasis and tumorigenesis. Additionally

CHIP can play its dual role as a tumor suppressor as well as an oncogene in numerous malignancies

thus acting as a double agent. Here

in this review

we have reported almost all substrates of CHIP established till date and classified them according to the hallmarks of cancer. In addition

we discussed about its architectural alignment

tissue specific expression

sub-cellular localization

folding-refolding mechanisms of client proteins

E4 ligase activity

normal physiological roles

as well as involvement in various diseases and tumor biology. Further

we aim to discuss its importance in HSP90 inhibitors mediated cancer therapy. Thus

this report concludes that CHIP may be a promising and worthy drug target towards pharmaceutical industry for drug development.