Hspbp1-flox Mouse

Hspbp1, also known as Hsp70-binding protein 1, is a co-chaperone belonging to a family that regulates Hsp70 activity [1,3,6]. It plays a crucial role in multiple cellular processes, such as protein folding, as it functions as a nucleotide exchange factor for Hsp70 molecular chaperones, facilitating the conversion from the ADP-bound to the ATP-bound state of Hsp70, thus closing the chaperone folding cycle [3,6]. It is involved in DNA repair, apoptosis, antiviral response, and the formation of stress granules, and is associated with diseases like breast cancer and HIV infection [1,2,4,5,7].

In breast cancer, in BRCA1-proficient cells, knocking down or overexpressing HspBP1 leads to profound changes in tumorigenesis, including in vitro anchorage-independent cell growth and in vivo tumor formation in xenograft models. It promotes BRCA1-mediated homologous recombination DNA repair by interacting with BRCA1, contributing to breast cancer suppression and genomic stability maintenance. However, it does not affect the tumorigenic properties in BRCA1-deficient cells. Additionally, regardless of BRCA1 status, HspBP1 facilitates cell survival in response to ionizing radiation by interfering with the association of Hsp70 and apoptotic protease-activating factor-1 [1]. In the antiviral response, knockdown and knockout of HSPBP1 lead to down-regulation of virus-induced RIG-I expression, inhibiting IRF3 activation and reducing the production of IFNB1, indicating that HSPBP1 positively regulates the antiviral signal pathway by inhibiting the K48-linked ubiquitination of RIG-I [2].

In conclusion, Hspbp1 is a multifunctional co-chaperone. Its role in DNA repair, apoptosis, and the antiviral response has been revealed through studies including gene-knockdown and knockout models. In breast cancer, it is closely related to BRCA1-associated tumorigenesis regulation, and in the antiviral field, it plays a positive role in the RLR-mediated antiviral response. These findings contribute to understanding the underlying mechanisms of related diseases and may provide potential therapeutic targets.