USP13

What is USP13 protein?

USP13 gene (ubiquitin specific peptidase 13) is a protein coding gene which situated on the long arm of chromosome 3 at locus 3q26. Enables several functions, including BAT3 complex binding activity; chaperone binding activity; and cysteine-type peptidase activity. Involved in several processes, including maintenance of unfolded protein involved in ERAD pathway; regulation of cellular catabolic process; and regulation of transcription, DNA-templated. Acts upstream of or within protein deubiquitination and protein stabilization. Predicted to be located in nucleoplasm. Predicted to be active in cytosol and nucleus. The USP13 protein is consisted of 863 amino acids and USP13 molecular weight is approximately 97.3 kDa.

What is the function of USP13 protein?

USP13 promotes the successful entry of cells into the M phase by stabilizing AuroraB and CDH1, which is critical for cell cycle regulation. In addition to its anti-apoptotic role in apoptosis, USP13 also has non-apoptotic functions such as regulatory roles in cell cycle, DNA damage response, autophagy, and endoplasmic reticulum quality control. USP13 plays a role in DNA damage response, protecting genomic stability and integrity by stabilizing effector molecules such as RAP80 and TopBP1. USP13 is associated with the process of autophagy, and it interacts with Beclin1 to promote autophagy by stabilizing the VPS34 complex, which is critical for cells to clear damaged and aging organelles. USP13 is involved in the endoplasmic reticulum associated degradation (ERAD) process, maintaining protein folding and degradation balance, and plays an important role in ER stress response.

Fig1. USP13 plays an anti-inflammatory role through the stabilization of Sigirr. (Lian Li, 2019)

USP13 Related Signaling Pathway

USP13 inhibits AKT signaling by deubiquitinating and stabilizing PTEN protein, thereby affecting cell growth and metabolism. PTEN is a tumor suppressor that controls cell growth and metabolism by inhibiting the AKT signaling pathway. USP13 interacts with PTEN to protect PTEN from proteasome degradation, thereby inhibiting tumor formation and glycolysis. USP13 is involved in DNA damage response, promoting BRCA1 recruitment and DNA repair through deubiquitination and stabilization of RAP80 protein. USP13 is involved in the endoplasmic reticulum associated degradation (ERAD) process, maintaining the balance of protein folding and degradation in the ER through deubiquitination and stabilization of associated substrate proteins. USP13 promotes the smooth progression of the cell cycle by deubiquitinating and stabilizing AuroraB and CDH1. The role of USP13 in cell cycle regulation is critical for cell proliferation and division.

USP13 Related Diseases

USP13 plays an important role in a variety of cancers, including lung, ovarian, cervical, hepatocellular, glioblastoma, melanoma, and stomach cancer. The role of USP13 in Alzheimer's disease (AD) and Parkinson's disease (PD) is closely related to the occurrence and development of neurodegenerative diseases. USP13 affects the antiviral response in viral infection by regulating the stability of STAT1 and STING. USP13 inhibits inflammation through past ubiquitination and stabilizes Sigirr and PTEN.

Bioapplications of USP13

USP13 inhibits the inflammatory response by regulating anti-inflammatory pathways, such as by stabilizing Sigirr and PTEN, which opens the possibility for the development of new anti-inflammatory drugs. The role of USP13 in modulating the antiviral response suggests that its inhibitors may help boost host defenses against viral infection. USP13's role in cell cycle regulation makes it potentially useful in cell biology research and the treatment of related diseases. The function of USP13 in response to DNA damage opens up the possibility of developing targeted therapies for specific genetic diseases or cancers. The deubiquitinating enzyme activity of USP13 makes it a promising target for drug development, especially the development of its specific inhibitors, such as Spautin-1, which have shown antitumor effects in preclinical models.