Dcun1d3-KO Mouse

DCUN1D3, also known as SCCRO3 or DCNL3, is a gene highly conserved among vertebrates. It plays a role in cell cycle regulation, specifically in the activation of SCFSKP2 ubiquitin E3 ligase activity and cell cycle progression. It is involved in the process of cullin-1 neddylation, which is crucial for the formation of the SCFSKP2 complex. This gene is also associated with the serum response element (SRE) pathway and is a novel UVC-responsive gene [1,2].

Knockdown of DCUN1D3 in cells leads to an increase in the cyclin-dependent kinase inhibitor p27 protein levels after UV irradiation, blocking the S phase progression. This occurs because the silence of DCUN1D3 inhibits the formation of the SCFSKP2 complex by reducing cullin-1 neddylation, as p27 is the primary target of this complex [1]. Over-expression of DCUN1D3 inhibits cell growth in HeLa cells, and when silenced by siRNA in UVC-treated HeLa cells, the cell cycle in the S phase is blocked, and UVC-induced cell death is inhibited [2]. Additionally, SCCRO3 (DCUN1D3) antagonizes the neddylation and oncogenic activity of SCCRO (DCUN1D1) by sequestering cullins to the membrane, blocking their nuclear translocation [3].

In conclusion, DCUN1D3 is essential for cell cycle progression and cell growth regulation, mainly through its role in cullin-1 neddylation and SCFSKP2 complex formation. The knockdown studies in cell lines have revealed its significance in UV-induced cell cycle responses and its potential as a tumor suppressor by antagonizing oncogenic neddylation processes [1,2,3].

References:

1. Zhang, Shuai, Huang, Jing, Shi, Taiping, Ma, Teng, Qiu, Xiaoyan. . DCUN1D3 activates SCFSKP2 ubiquitin E3 ligase activity and cell cycle progression under UV damage. In Oncotarget, 7, 58483-58491. doi:10.18632/oncotarget.11302. https://pubmed.ncbi.nlm.nih.gov/27542266/

2. Ma, Teng, Shi, Taiping, Huang, Jing, Ma, Dalong, Qiu, Xiaoyan. 2008. DCUN1D3, a novel UVC-responsive gene that is involved in cell cycle progression and cell growth. In Cancer science, 99, 2128-35. doi:10.1111/j.1349-7006.2008.00929.x. https://pubmed.ncbi.nlm.nih.gov/18823379/

3. Huang, Guochang, Stock, Cameron, Bommeljé, Claire C, Ramanathan, Suresh Y, Singh, Bhuvanesh. 2014. SCCRO3 (DCUN1D3) antagonizes the neddylation and oncogenic activity of SCCRO (DCUN1D1). In The Journal of biological chemistry, 289, 34728-42. doi:10.1074/jbc.M114.585505. https://pubmed.ncbi.nlm.nih.gov/25349211/