Squamous Cell Carcinoma-related Oncogene (SCCRO) Family Members Regulate Cell Growth and Proliferation through Their Cooperative and Antagonistic Effects on Cullin Neddylation.

The Journal of Biological Chemistry
Weimin FuBhuvanesh Singh

Abstract

SCCRO (squamous cell carcinoma-related oncogene; also known as DCUN1D1) is a highly conserved gene that functions as an E3 in neddylation. Although inactivation of SCCRO in yeast results in lethality, SCCRO(-/-) mice are viable. The exclusive presence of highly conserved paralogues in higher organisms led us to assess whether compensation by SCCRO paralogues rescues lethality in SCCRO(-/-) mice. Using murine and Drosophila models, we assessed the in vivo activities of SCCRO and its paralogues in cullin neddylation. We found that SCCRO family members have overlapping and antagonistic activity that regulates neddylation and cell proliferation activities in vivo. In flies, both dSCCRO and dSCCRO3 promote neddylation and cell proliferation, whereas dSCCRO4 negatively regulates these processes. Analysis of somatic clones showed that the effects that these paralogues have on proliferation serve to promote cell competition, leading to apoptosis in clones with a net decrease in neddylation activity. We found that dSCCRO and, to a lesser extent, dSCCRO3 rescue the neddylation and proliferation defects promoted by expression of SCCRO4. dSCCRO and dSCCRO3 functioned cooperatively, with their coexpression resulting in an increase in both t...Continue Reading

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Citations

Jul 26, 2019·Journal of Dental Research·H Q LiaoZ G Cao
Jan 18, 2019·PloS One·Guochang HuangBhuvanesh Singh
Jun 6, 2017·Nature Chemical Biology·Daniel C ScottR Kip Guy
Aug 12, 2020·Nature Reviews. Genetics·Nicholas E Baker
Oct 8, 2020·The FEBS Journal·Tao Zou, Jiyan Zhang
Apr 17, 2021·Pathology, Research and Practice·Ilenia ChatziandreouAngelica A Saetta
Aug 30, 2019·Journal of Medicinal Chemistry·Ho Shin KimR Kiplin Guy

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