Heat shock protein 105 (HSP105)

Heat shock protein 105 (HSP105, also known as Hsp110, encoded by HSPH1) is a large molecular chaperone in the Hsp70 superfamily, most highly abundant in brain and multiple other tissues[1][3]. It functions as both a nucleotide exchange factor for chaperones like Hsc70 and a holdase to prevent aggregation of denatured or misfolded proteins under stress conditions, helping maintain protein homeostasis and promote cell survival[1][3]. HSP105 can be highly induced by multiple proteotoxic stresses, is cytoprotective, and has a pivotal role in apoptosis regulation and immune modulation by presenting protein antigens for immune responses[1][2]. Overexpression of HSP105 is linked to cancer cell survival, chemoresistance, and has also been observed in neurodegeneration and inflammatory conditions[1][2]. Pharmacological modulation or targeted therapies (e.g., siRNA) may have therapeutic potential in oncology and neuroprotection, but systemic manipulation poses safety and specificity challenges[1][2].

Other names

HSP105Hsp110Heat shock 105kD proteinHSPH1Hsp105αHsp105β

Small interfering RNA (siRNA): suppression of HSP105 expression leads to cancer cell apoptosis through caspase-mediated mechanisms (independent of p53). Induction by small molecules (e.g., celastrol): upregulation of HSP105 confers cytoprotection in injury models.