STIP1 - Stress induced phosphoprotein 1 | Elisa - Clia - Antibody - Protein

Background

Stress-induced phosphoprotein 1 (STIP1), also known as heat shock protein-organizing protein (HOP), is a co-chaperone protein that plays a pivotal role in protein folding, stabilization, and assembly. It is induced under stress conditions to aid in the maintenance of protein homeostasis. STIP1 interacts with various heat shock proteins (HSPs), particularly HSP70 and HSP90, facilitating the transfer of client proteins between these chaperones. This protein is crucial for the proper functioning of the chaperone machinery, which is essential for cellular survival under stress conditions. Dysregulation of STIP1 is implicated in several diseases, including neurodegenerative disorders and cancer.

Protein Structure

STIP1 is composed of several tetratricopeptide repeat (TPR) domains, which are important for its function:

• TPR1 Domain: This domain interacts with the C-terminal of HSP70.
• TPR2A and TPR2B Domains: These domains are involved in binding to HSP90, facilitating the transfer of client proteins.
• DP1 Domain: Located between TPR2A and TPR2B, this domain contributes to the structural stability of the protein.
• TPR2A/DP2: This composite region is crucial for the coordinated interaction with HSP90 and HSP70.

Classification and Subtypes

STIP1 belongs to the family of tetratricopeptide repeat (TPR) domain-containing proteins, which are characterized by their role in protein-protein interactions, especially in the context of chaperone function. STIP1 is one of the key members of this family, functioning primarily as a co-chaperone.

Function and Biological Significance

STIP1 plays several critical roles in cellular processes:

• Chaperone Activity: STIP1 acts as a co-chaperone, mediating the interaction between HSP70 and HSP90, ensuring efficient client protein folding and stabilization.
• Protein Transport: Facilitates the transfer of partially folded client proteins from HSP70 to HSP90, which is essential for the maturation of several regulatory and signaling proteins.
• Stress Response: Upregulated in response to cellular stress, STIP1 helps in maintaining protein homeostasis by preventing the aggregation of misfolded proteins.
• Signal Transduction: Through its interaction with various client proteins, STIP1 is involved in modulating signaling pathways, which can affect cell growth, differentiation, and apoptosis.

Clinical Issues

Abnormal expression or mutations in STIP1 have been linked to various diseases:

• Neurodegenerative Diseases: Given its role in protein homeostasis, dysregulation of STIP1 is implicated in diseases like Alzheimer's and Parkinson's, where protein misfolding and aggregation are key features.
• Cancer: Overexpression of STIP1 has been observed in several types of cancers, including breast, ovarian, and colorectal cancer, where it may contribute to tumorigenesis by stabilizing oncogenic proteins and promoting cell survival under stress conditions.
• Infectious Diseases: STIP1 plays a role in the immune response to infections by stabilizing key signaling proteins involved in pathogen recognition and response.

Summary

Stress-induced phosphoprotein 1 (STIP1) is a critical co-chaperone that facilitates the interaction between HSP70 and HSP90, ensuring proper protein folding and stabilization under stress conditions. It consists of several TPR domains that mediate its interactions with heat shock proteins. STIP1 is involved in essential cellular processes, including the stress response and signal transduction. Dysregulation of STIP1 is associated with neurodegenerative diseases, cancer, and infectious diseases, highlighting its importance in maintaining cellular homeostasis and its potential as a therapeutic target.