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The Regulation of Cellular Proliferation by VACM‐1/CUL5 is Dependent on its Posttranslational Modifications by NEDD8
Author(s) -
Sundquist Skylar Paige,
Lee Si Eun,
BurnatowskaHledin Maria
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.461.21
Subject(s) - neddylation , nedd8 , microbiology and biotechnology , mutant , ubiquitin ligase , biology , cell cycle , ubiquitin , apoptosis , biochemistry , gene
VACM‐1/CUL5 acts as the scaffold protein in the E3 ligase complex in the ubiquitin‐dependent protein degradation pathway. The overexpression of VACM‐1/CUL5 is known to inhibit proliferation, whereas inhibition of VACM‐1/CUL5 expression induces cellular proliferation. Thus, VACM‐1/CUL5 is implicated in cancer pathways. The effect of VACM‐1/CUL5 on cellular proliferation is dependent on its post‐translational modification (PTM) by NEDD8 protein (neddylation). The relationship between NEDD8 and VACM‐1/CUL5 is important for cell cycle regulation and offers a target for cancer therapy. This work explores the structure‐function relationship between VACM‐1/CUL5 and its neddylation. VACM‐1/CUL5 was mutated at the putative neddylation site Lysine (K) 724 and at three potential neddylation sites, K724, K727, and K728 (3K mutant). Our work suggests that the expression of the K724 mutant induces growth whereas expression of the 3K mutant does not affect cell growth. Interestingly, Western Blot analysis indicates that the 3K VACM‐1/CUL5 mutant is still neddylated, which suggests that VACM‐1/CUL5 may be neddylated at additional lysine sites. Our current work focuses on characterizing cells transfected with the mutated VACM‐1/CUL5 cDNAs to elucidate how site‐specific neddylation may control alternative signaling pathways. Support or Funding Information This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .