title: DCUN1D3 activates SCFSKP2 ubiquitin E3 ligase activity and cell cycle progression under UV damage.
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 SCFSKP2 complex by reducing Cullin-1 neddylation. Given that p27 is the primary target of SCFSKP2 complex, the cells lost DCUN1D3 showed a remarkable accumulation of p27 to cause S phase block.
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, China.|Chinese National Human Genome Center, Beijing, China.
authors.forename: Taiping
authors.initials: T
authors.lastname: Shi
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: Fanlei
authors.initials: F
authors.lastname: Hu
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Radiation Toxicology and Oncology, Beijing Key Laboratory for Radiobiology (BKLRB), Beijing Institute of Radiation Medicine, Beijing, P. R. China.
authors.forename: Ping-Kun
authors.initials: PK
authors.lastname: Zhou
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: Dalong
authors.initials: D
authors.lastname: Ma
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, China.|Department of Radiation Toxicology and Oncology, Beijing Key Laboratory for Radiobiology (BKLRB), Beijing Institute of Radiation Medicine, Beijing, P. R. China.
authors.forename: Teng
authors.initials: T
authors.lastname: Ma
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Qiu
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D011485:Protein Binding; D016196:S Phase; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism*; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: C486317:CAND1 protein, human; C436291:CDKN1B protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C534519:DCUN1D3 protein, human; C479529:RBX1 protein, human; D044786:S-Phase Kinase-Associated Proteins; D014157:Transcription Factors; D050760:Cyclin-Dependent Kinase Inhibitor p27; D044843:SKP Cullin F-Box Protein Ligases; D044767:Ubiquitin-Protein Ligases; D005982:Glutathione Transferase
keywords: CAND1; DCUN1D3; SCFSKP2; cell cycle; p27