Hypoxia up-regulated protein 1 (HYOU1), Heat shock protein 90kDa alpha family class B member 1 (HSP90AB1), and Heat shock protein family A (Hsp70) member 8 (HSPA8) (HYOU1, HSP90AB1, HSPA8)

The target group comprising HYOU1, HSP90AB1, and HSPA8 represents a functional subset of the molecular chaperome essential for cellular proteostasis. HYOU1 (Hypoxia Up-Regulated 1), also known as ORP150, is an endoplasmic reticulum-resident chaperone that plays a critical role in protein folding and cytoprotection under hypoxic stress (UniProt Q9Y4L1). HSP90AB1 (Heat Shock Protein 90 Alpha Family Class B Member 1) is a constitutively expressed cytosolic chaperone that stabilizes numerous client proteins, including oncogenic kinases and transcription factors, making it a prominent target in oncology (UniProt P08238; Nature Reviews Molecular Cell Biology, 2016). HSPA8 (Heat Shock Protein Family A Member 8), or Hsc70, is a cognate chaperone involved in the folding of nascent polypeptides, clathrin-mediated endocytosis, and chaperone-mediated autophagy (UniProt P11142; Frontiers in Pharmacology, 2020). These chaperones often form high-molecular-weight complexes, sometimes termed epichaperomes, which are particularly active in cancer cells to maintain the stability of mutated or overexpressed proteins (Nature, 2016). Therapeutic targeting of these proteins, primarily through HSP90 inhibitors like Ganetespib and Tanespimycin, disrupts their ATPase activity, leading to the degradation of client proteins and subsequent cell death (Journal of Hematology & Oncology, 2019).

Other names

Hypoxia up-regulated protein 1 (HYOU1)Heat shock protein 90kDa alpha family class B member 1 (HSP90AB1)Heat shock protein family A (Hsp70) member 8 (HSPA8)ORP150GRP170HSP12AHSP90BHSPCBHSP90-betaHsc70Hsc71HSP7CLAP1

Inhibition of the ATPase activity of the chaperone proteins, which prevents the stabilization and folding of client proteins, leading to their ubiquitination and subsequent degradation by the proteasome.