KCTD10 is involved in the cardiovascular system and Notch signaling during early embryonic development.
As a member of the polymerase delta-interacting protein 1 (PDIP1) gene family, potassium channel tetramerisation domain-containing 10 (KCTD10) interacts with proliferating cell nuclear antigen (PCNA) and polymerase δ, participates in DNA repair, DNA replication and cell-cycle control. In order to further investigate the physiological functions of KCTD10, we generated the KCTD10 knockout mice. The heterozygous KCTD10(+/-) mice were viable and fertile, while the homozygous KCTD10(-/-) mice showed delayed growth from E9.0, and died at approximately E10.5, which displayed severe defects in angiogenesis and heart development. Further study showed that VEGF induced the expression of KCTD10 in a time- and dose-dependent manner. Quantitative real-time PCR and western blotting results revealed that several key members in Notch signaling were up-regulated either in KCTD10-deficient embryos or in KCTD10-silenced HUVECs. Meanwhile, the endogenous immunoprecipitation (IP) analysis showed that KCTD10 interacted with Cullin3 and Notch1 simultaneously, by which mediating Notch1 proteolytic degradation. Our studies suggest that KCTD10 plays crucial roles in embryonic angiogenesis and heart development in mammalians by negatively regulating the Notch signaling pathway.
Key Laboratory of Protein Chemistry and Developmental Biology of State Education Ministry of China, College of Life Science, Hunan Normal University, Changsha, P. R. China; Model Animal Research Center, MOE Key Laboratory of Model Animal for Disease Research, Medical School, Nanjing University, Nanjing, P.R. China; College of Medicine, Hunan Normal University, Changsha, P. R. China.
Kaiqun
K
Ren
Key Laboratory of Protein Chemistry and Developmental Biology of State Education Ministry of China, College of Life Science, Hunan Normal University, Changsha, P. R. China.
Jing
J
Yuan
Key Laboratory of Protein Chemistry and Developmental Biology of State Education Ministry of China, College of Life Science, Hunan Normal University, Changsha, P. R. China.
Manjun
M
Yang
Model Animal Research Center, MOE Key Laboratory of Model Animal for Disease Research, Medical School, Nanjing University, Nanjing, P.R. China.
Xiang
X
Gao
Key Laboratory of Protein Chemistry and Developmental Biology of State Education Ministry of China, College of Life Science, Hunan Normal University, Changsha, P. R. China.
Xiaofeng
X
Ding
Key Laboratory of Protein Chemistry and Developmental Biology of State Education Ministry of China, College of Life Science, Hunan Normal University, Changsha, P. R. China.
Jianlin
J
Zhou
Key Laboratory of Protein Chemistry and Developmental Biology of State Education Ministry of China, College of Life Science, Hunan Normal University, Changsha, P. R. China.
Xingwang
X
Hu
College of Medicine, Hunan Normal University, Changsha, P. R. China.
Jianguo
J
Cao
College of Medicine, Hunan Normal University, Changsha, P. R. China.
Xiyun
X
Deng
Key Laboratory of Protein Chemistry and Developmental Biology of State Education Ministry of China, College of Life Science, Hunan Normal University, Changsha, P. R. China.
Shuanglin
S
Xiang
Key Laboratory of Protein Chemistry and Developmental Biology of State Education Ministry of China, College of Life Science, Hunan Normal University, Changsha, P. R. China.
Jian
J
Zhang
D000818:Animals; D002319:Cardiovascular System / Q000196:embryology* / Q000378:metabolism*; D002460:Cell Line; D044842:Cullin Proteins / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D023061:Gene Order; D005804:Genes, Lethal; D056426:Genetic Loci; D006330:Heart Defects, Congenital / Q000235:genetics / Q000473:pathology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000235:genetics; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D059748:Proteolysis; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
C503646:Cul3 protein, mouse; D044842:Cullin Proteins; C543439:KCTD10 protein, mouse; D024642:Potassium Channels, Voltage-Gated; D051880:Receptors, Notch; D042461:Vascular Endothelial Growth Factor A