STIP1

STIP1, or stress-induced-phosphoprotein 1, is a conserved co-chaperone of the eukaryotic HSP70/HSP90 chaperone system. In humans, the STIP1 gene encodes the STIP1 protein, which is also known as HOP (HSP70-HSP90 organizing protein). The protein contains three tetratricopeptide repeat (TPR) domains that mediate interactions with the C-terminal EEVD motifs of HSP70 and HSP90, enabling the transfer of client proteins between these chaperones.

Functionally, STIP1 acts as a scaffold that coordinates the HSP70 and HSP90 chaperone cycles, promoting maturation, activation, and stabilization of a wide range of client proteins. It plays a crucial role in the folding and activation of steroid hormone receptors and other signaling proteins, contributing to cellular proteostasis under normal and stress conditions.

Localization of STIP1 is predominantly cytosolic, with ubiquitous expression across tissues. Its activity can be modulated by cellular stress and post-translational modifications such as phosphorylation, reflecting its role in dynamic chaperone responses.

In research and clinical contexts, STIP1 is studied for its involvement in cancer biology and neurodegenerative diseases, where chaperone networks influence protein homeostasis and signaling pathways. Ongoing investigations aim to define its full client repertoire, regulatory mechanisms, and potential as a therapeutic target within the HSP70/HSP90 chaperone system.