Squamous cell carcinoma-related oncogene (SCCRO) family members regulate cell growth and proliferation through their cooperative and antagonistic effects on cullin neddylation Journal Article


Authors: Fu, W.; Sun, J.; Huang, G.; Liu, J. C.; Kaufman, A.; Ryan, R. J. H.; Ramanathan, S. Y.; Venkatesh, T.; Singh, B.
Article Title: Squamous cell carcinoma-related oncogene (SCCRO) family members regulate cell growth and proliferation through their cooperative and antagonistic effects on cullin neddylation
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.Wefound 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 the neddylated cullin fraction and proliferation activity. In contrast, human SCCRO and SCCRO4 promote, and human SCCRO3 inhibits, neddylation and proliferation when expressed in flies. Our findings provide the first insights into the mechanisms through which SCCRO family members cooperatively regulate neddylation and cell proliferation. ©2016 by The American Society for Biochemistry and Molecular Biology, Inc.
Keywords: squamous cell carcinoma; cell proliferation; cytology; cell death; in-vivo; mammals; clone cells; cells; cloning; cell competition; antagonistic activity; antagonistic effects; co-expression; proliferation activity
Journal Title: Journal of Biological Chemistry
Volume: 291
Issue: 12
ISSN: 0021-9258
Publisher: American Society for Biochemistry and Molecular Biology  
Date Published: 2016-03-18
Start Page: 6200
End Page: 6217
Language: English
DOI: 10.1074/jbc.M115.692756
PROVIDER: scopus
PMCID: PMC4813546
PUBMED: 26792857
DOI/URL:
Notes: Article -- Export Date: 2 June 2016 -- Source: Scopus
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MSK Authors
  1. Russell J H Ryan
    5 Ryan
  2. Bhuvanesh Singh
    217 Singh
  3. Jeffrey Chang-Jen Liu
    7 Liu
  4. Guochang Huang
    15 Huang
  5. Weimin Fu
    4 Fu