Hs1bp3-KO Mouse

Hs1bp3, also known as HCLS1 binding protein 3, is a protein-coding gene with significant functions in multiple biological processes. It contains several important segments like a PX domain, a leucine zipper, and may be involved in lymphocyte activation [5]. It also has a role in regulating autophagy, a crucial membrane trafficking and intracellular degradation process [1,3,4].

In autophagy, HS1BP3 acts as a negative regulator of autophagosome formation. Depletion of HS1BP3 in human cells and zebrafish increases the formation of LC3-positive autophagosomes [1,4]. HS1BP3 localizes to autophagosome precursors and binds phosphatidic acid (PA) through its PX domain. When HS1BP3 is depleted, the total cellular PA content is upregulated due to increased activity of PLD1 and its localization to ATG16L1-positive membranes, suggesting HS1BP3 regulates autophagy by modulating PA content in autophagosome precursor membranes [1,3,4]. In hepatocellular carcinoma, high expression of HS1BP3 is associated with poor prognosis, and its silencing inhibits proliferation, invasion, and migration of HCC cells. Estrogen receptor 1 (ESR1) can inhibit HCC proliferation and improve prognosis by interacting with the HS1BP3 promoter [2].

In conclusion, HS1BP3 has a negative regulatory function in autophagy through modulating membrane lipids, and it promotes hepatocellular carcinoma progression. The study of HS1BP3 in model organisms like human cells and zebrafish has provided insights into its role in autophagy regulation and cancer-related processes, which may help in understanding the underlying mechanisms of these biological functions and diseases [1,2,4].

References:

1. Søreng, Kristiane, Knævelsrud, Helene, Holland, Petter, Simonsen, Anne. 2017. HS1BP3 inhibits autophagy by regulation of PLD1. In Autophagy, 13, 985-986. doi:10.1080/15548627.2017.1291483. https://pubmed.ncbi.nlm.nih.gov/28318354/

2. Hu, Xiaosi, Pan, Hongtao, Zhou, Shuai, Jin, Hao, Xu, Aman. 2022. HS1BP3, transcriptionally regulated by ESR1, promotes hepatocellular carcinoma progression. In Biochemical and biophysical research communications, 623, 111-119. doi:10.1016/j.bbrc.2022.07.047. https://pubmed.ncbi.nlm.nih.gov/35921704/

3. Yin, Zhangyuan, Klionsky, Daniel J. 2017. HS1BP3 provides a novel mechanism of negative autophagy regulation through membrane lipids. In Autophagy, 13, 779-780. doi:10.1080/15548627.2017.1305534. https://pubmed.ncbi.nlm.nih.gov/28323521/

4. Holland, Petter, Knævelsrud, Helene, Søreng, Kristiane, Di Paolo, Gilbert, Simonsen, Anne. 2016. HS1BP3 negatively regulates autophagy by modulation of phosphatidic acid levels. In Nature communications, 7, 13889. doi:10.1038/ncomms13889. https://pubmed.ncbi.nlm.nih.gov/28004827/

5. Takemoto, Y, Furuta, M, Sato, M, Kubo, M, Hashimoto, Y. . Isolation and characterization of a novel HS1 SH3 domain binding protein, HS1BP3. In International immunology, 11, 1957-64. doi:. https://pubmed.ncbi.nlm.nih.gov/10590261/