DCUN1D3 activates SCF SKP2  ubiquitin E3 ligase activity and cell cycle progression under UV damage

Shuai Zhang; Jing Huang; Taiping Shi; Fanlei Hu; Li Zhang; Ping-Kun Zhou; Dalong Ma; Teng Ma; Xiaoyan Qiu

doi:10.18632/oncotarget.11302

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Research Papers:

DCUN1D3 activates SCF^SKP2 ubiquitin E3 ligase activity and cell cycle progression under UV damage

Shuai Zhang, Jing Huang, Taiping Shi, Fanlei Hu, Li Zhang, Ping-Kun Zhou, Dalong Ma, Teng Ma and Xiaoyan Qiu _

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Oncotarget. 2016; 7:58483-58491. https://doi.org/10.18632/oncotarget.11302

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Abstract

Shuai Zhang1, Jing Huang1, Taiping Shi1,2, Fanlei Hu1, Li Zhang1, Ping-Kun Zhou3, Dalong Ma1, Teng Ma1,3, Xiaoyan Qiu1

1Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, China

2Chinese National Human Genome Center, Beijing, China

3Department of Radiation Toxicology and Oncology, Beijing Key Laboratory for Radiobiology (BKLRB), Beijing Institute of Radiation Medicine, Beijing, P. R. China

Correspondence to:

Xiaoyan Qiu, email: [email protected]

Teng Ma, email: [email protected]

Keywords: DCUN1D3, CAND1, SCF^SKP2, p27, cell cycle

Received: January 24, 2016 Accepted: July 26, 2016 Published: August 16, 2016

ABSTRACT

Our previous study showed that knockdown the endogenous expression of DCUN1D3 (also called SCCRO3 or DCNL3) blocked the S phase progression after UV irradiation. Here, we show that the silence of DCUN1D3 can increase the cyclin-dependent kinase inhibitor p27 protein levels after UV irradiation. Through Co-immunoprecipitation experiments, we found that DCUN1D3 bound to CAND1. And DCUN1D3 knockdown synergized with CAND1 over-expression in arresting the S phase. Given the CAND1’s established role in Cullin-1 neddylation, we found Cullin-1 was less neddylated in DCUN1D3 deficient cells. So the silence of DCUN1D3 can inhibit the formation of SCF^SKP2 complex by reducing Cullin-1 neddylation. Given that p27 is the primary target of SCF^SKP2 complex, the cells lost DCUN1D3 showed a remarkable accumulation of p27 to cause S phase block.

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Research Papers:

DCUN1D3 activates SCFSKP2 ubiquitin E3 ligase activity and cell cycle progression under UV damage

Abstract

DCUN1D3 activates SCF^SKP2 ubiquitin E3 ligase activity and cell cycle progression under UV damage