St13-KO Mouse

St13, also known as the gene encoding Hsp70 interacting protein (Hip), is a co-factor (co-chaperone) of the 70-kDa heat shock proteins (Hsc/Hsp70). It collaborates with other co-factors to facilitate the chaperone function of Hsc/Hsp70 in protein folding, repair, and in controlling regulatory proteins' activity. It is involved in various biological processes, and its study using genetic models can provide insights into its functions [2].

In a CP (chronic pancreatitis) model, knockout of St13 exacerbated fatty replacement and fibrosis. St13 binds Sdf2l1 to regulate the arachidonic acid (AA) pathway, protecting against the cellular characteristics of CP [1]. In colorectal cancer cell lines, overexpression of ST13 inhibited cell proliferation, colony formation, and cell migration in vitro, while down-regulation of ST13 increased cell proliferation, cloning efficiency in vitro, and tumorigenicity in vivo, indicating it as a proliferation regulator in CRC [3]. In pancreatic ductal adenocarcinoma, ST13 expression was lower in cancer tissues, and an oncolytic adenovirus expressing ST13 enhanced the antitumor effect of TRAIL [4]. A pilot study found that polymorphism in ST13 was associated with the risk of ischemic stroke, specifically in females [5].

In conclusion, St13 plays essential roles in protein-related functions through its co-chaperone activity. Model-based research, especially gene knockout studies, has revealed its significance in diseases such as chronic pancreatitis, colorectal cancer, pancreatic adenocarcinoma, and ischemic stroke, providing valuable insights into disease mechanisms and potential therapeutic targets.

References:

1. Cao, Rong-Chang, Yang, Wan-Jun, Xiao, Wang, Zhou, Jie, Zhang, Guo-Wei. 2022. St13 protects against disordered acinar cell arachidonic acid pathway in chronic pancreatitis. In Journal of translational medicine, 20, 218. doi:10.1186/s12967-022-03413-8. https://pubmed.ncbi.nlm.nih.gov/35562743/

2. Shi, Zheng-zheng, Zhang, Jia-wei, Zheng, Shu. . What we know about ST13, a co-factor of heat shock protein, or a tumor suppressor? In Journal of Zhejiang University. Science. B, 8, 170-6. doi:. https://pubmed.ncbi.nlm.nih.gov/17323428/

3. Bai, Rui, Shi, Zhong, Zhang, Jia-wei, Zhu, Yong-liang, Zheng, Shu. . ST13, a proliferation regulator, inhibits growth and migration of colorectal cancer cell lines. In Journal of Zhejiang University. Science. B, 13, 884-93. doi:10.1631/jzus.B1200037. https://pubmed.ncbi.nlm.nih.gov/23125081/

4. Zhang, Youni, Ye, Miaojuan, Huang, Fang, Mou, Xiaozhou, Wang, Yigang. 2020. Oncolytic Adenovirus Expressing ST13 Increases Antitumor Effect of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Against Pancreatic Ductal Adenocarcinoma. In Human gene therapy, 31, 891-903. doi:10.1089/hum.2020.024. https://pubmed.ncbi.nlm.nih.gov/32475172/

5. Stetskaya, T A, Krapiva, A B, Kobzeva, K A, Polonikov, A V, Bushueva, O Yu. 2024. Polymorphism in Genes Encoding Adaptor Proteins ST13 and STIP1 and the Risk of Ischemic Stroke: a Pilot Study. In Bulletin of experimental biology and medicine, 176, 477-480. doi:10.1007/s10517-024-06050-x. https://pubmed.ncbi.nlm.nih.gov/38492099/