Stress-induced-phosphoprotein 1 (STIP1) (STIP1)

Stress-induced-phosphoprotein 1 (STIP1), also known as Hsp70-Hsp90 organizing protein (HOP), is a critical co-chaperone that acts as an adaptor to coordinate the transfer of client proteins between the Hsp70 and Hsp90 chaperone systems [1, 2]. It contains multiple tetratricopeptide repeat (TPR) domains that mediate its interaction with the C-terminal motifs of these heat shock proteins, thereby regulating protein folding and maturation [2, 13]. STIP1 is frequently overexpressed in various malignancies, including ovarian, pancreatic, and breast cancers, where it promotes tumor cell proliferation, migration, and invasion through the activation of oncogenic signaling pathways such as JAK2-STAT3 and PI3K-AKT [3, 4, 16]. Beyond its intracellular role, STIP1 can be secreted into the extracellular space and function as a signaling molecule by binding to receptors like ALK2 and the cellular prion protein (PrPC) [4, 14]. Due to its central role in maintaining the stability of numerous oncoproteins and its association with poor prognosis, STIP1 is being investigated as a therapeutic target using inhibitory peptides, antibodies, and small molecules designed to disrupt its chaperone-organizing function [3, 12].

Other names

HOPSTI1STI1LHsc70/Hsp90-organizing proteinP60HEL-S-94nIEF-SSP-3521

Inhibition of the Hsp70-Hsp90 chaperone cycle by disrupting the interaction between STIP1 and heat shock proteins, leading to the degradation of client oncoproteins and induction of apoptosis.