Psmd10, also known as Gankyrin, p28, or p28GANK, is a proteasomal chaperone and oncoprotein. It is associated with the proteasome and plays a role in multiple biological processes. Overexpression of Psmd10 is linked to poor prognosis in many cancers, and it may be involved in pathways related to cancer development, autophagy, and endoplasmic reticulum stress [1,2,3,4]. Genetically modified mouse models are valuable for studying its in-vivo functions.

In vivo studies using gene-knockout (KO) mouse models have provided insights into Psmd10's role. Mice with liver parenchymal cell-specific gankyrin ablation (Alb-Cre;gankyrinf/f) and gankyrin deletion both in liver parenchymal and in non-parenchymal cells (Mx1-Cre;gankyrinf/f) showed reduced STAT3 activity, interleukin-6 production, and cancer stem cell marker expression, leading to attenuated tumorigenic potential in the diethylnitrosamine hepatocarcinogenesis model. Similar results were obtained in the colitis-associated cancer model using mice with intestinal epithelial cell-specific gankyrin ablation (Villin-Cre;Gankyrinf/f) and gankyrin deletion both in myeloid and epithelial cells (Mx1-Cre;Gankyrinf/f). These findings indicate important roles of Psmd10 in non-parenchymal cells as well as parenchymal cells in the pathogenesis of liver cancers and colorectal cancers [2].

In conclusion, Psmd10 is an oncoprotein with a crucial role in the pathogenesis of various cancers. The KO/CKO mouse models have revealed its significance in the tumorigenesis of liver and colorectal cancers, suggesting that targeting Psmd10 could be a promising strategy for cancer therapy.

References:

1. M G, Mukund Sudharsan, Chikhale, Rupesh, Nanaware, Padma P, Dalvi, Somavally, Venkatraman, Prasanna. 2021. A druggable pocket on PSMD10Gankyrin that can accommodate an interface peptide and doxorubicin. In European journal of pharmacology, 915, 174718. doi:10.1016/j.ejphar.2021.174718. https://pubmed.ncbi.nlm.nih.gov/34953804/

2. Fujita, Jun, Sakurai, Toshiharu. . The Oncoprotein Gankyrin/PSMD10 as a Target of Cancer Therapy. In Advances in experimental medicine and biology, 1164, 63-71. doi:10.1007/978-3-030-22254-3_5. https://pubmed.ncbi.nlm.nih.gov/31576540/

3. Luo, Tao, Fu, Jing, Xu, An, Chen, Yao, Wang, Hongyang. 2015. PSMD10/gankyrin induces autophagy to promote tumor progression through cytoplasmic interaction with ATG7 and nuclear transactivation of ATG7 expression. In Autophagy, 12, 1355-71. doi:10.1080/15548627.2015.1034405. https://pubmed.ncbi.nlm.nih.gov/25905985/

4. Li, Jianwei, Tian, Feng, Li, Dajiang, Li, Xiaowu, Wang, Shuguang. 2014. MiR-605 represses PSMD10/Gankyrin and inhibits intrahepatic cholangiocarcinoma cell progression. In FEBS letters, 588, 3491-500. doi:10.1016/j.febslet.2014.08.008. https://pubmed.ncbi.nlm.nih.gov/25131931/