Hbp1, also known as HMG box protein 1, is a transcription factor that functions as a potent cell cycle inhibitor in normal and cancer cells. It is involved in various biological processes, including cell cycle regulation, cell differentiation, and senescence. Hbp1 can activate or repress the expression of different cell cycle genes through direct DNA binding, cofactor recruitment, chromatin remodeling, or neutralization of other transcription factors. It is also part of signaling pathways such as the WNT/β -catenin pathway, and its expression is regulated by micro -RNAs and the phosphatidylinositol-3 kinase (PI3K)/AKT pathway [1].

In hepatoma, Hbp1 -mediated transcriptional repression of alpha -fetoprotein (AFP) inhibits hepatoma progression, as Hbp1 can directly bind to the AFP gene promoter to repress its expression [2]. In breast cancer, the Hbp1/TIMP3 axis plays a crucial role in inhibiting tumorigenesis, where Hbp1 enhances TIMP3 promoter activity, and deletion of Hbp1 induces breast cancer occurrence and malignant progression [3]. In type 2 diabetes mellitus, Hbp1 deficiency in mice aggravates diabetes features as Hbp1 activates the transcription of the IGFBP1 gene, forming an insulin/Hbp1/IGFBP1 negative feedback loop to regulate blood glucose and insulin concentrations [4]. In chicken preadipocytes, knockout of Hbp1 inhibits their proliferation, while overexpression promotes it, with Hbp1 directly repressing SOCS3 transcription to regulate this process [5]. In nucleus pulposus cells, Hbp1 gene overexpression increases senescence-related p16 expression, affects cell proliferation and apoptosis, and Hbp1 deficiency protects against stress-induced premature senescence [6].

In conclusion, Hbp1 is a key transcription factor involved in cell cycle regulation, differentiation, and senescence. Its study through gene knockout or other loss-of-function models has revealed its importance in various diseases, including cancer and type 2 diabetes mellitus. Understanding Hbp1 function provides potential therapeutic targets for these diseases.