C/EBPδ (CCAAT/enhancer-binding protein δ) is a member of the C/EBP family of nuclear proteins that function in the control of cell growth, survival, differentiation and apoptosis. We previously demonstrated that C/EBPδ gene transcription is highly induced in G0 growth-arrested mammary epithelial cells but the C/EBPδ protein exhibits a t1/2 of only ∼120 min. The goal of the present study was to investigate the role of C/EBPδ modification by ubiquitin and C/EBPδ proteasome-mediated degradation. Structural and mutational analyses demonstrate that an intact leucine zipper is required for C/EBPδ ubiquitination; however, the leucine zipper does not provide lysine residues for ubiquitin conjugation. C/EBPδ ubiquitination is not required for proteasome-mediated C/EBPδ degradation and the presence of ubiquitin does not increase C/EBPδ degradation by the proteasome. Instead, the leucine zipper stabilizes the C/EBPδ protein by forming homodimers that are poor substrates for proteasome degradation. To investigate the cellular conditions associated with C/EBPδ ubiquitination we treated G0 growth-arrested mammary epithelial cells with DNA-damage- and oxidative-stress-inducing agents and found that C/EBPδ ubiquitination is induced in response to H2O2. However, C/EBPδ protein stability is not influenced by H2O2 treatment. In conclusion, our results demonstrate that proteasome-mediated protein degradation of C/EBPδ is ubiquitin-independent.
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Research Article|
June 27 2007
Proteasome-mediated CCAAT/enhancer-binding protein δ (C/EBPδ) degradation is ubiquitin-independent
Shanggen Zhou;
Shanggen Zhou
1The Ohio State Biochemistry Program, Department of Veterinary Biosciences, The Ohio State University, 1925 Coffey Road, Columbus, OH 43210-1093, U.S.A.
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James W. DeWille
James W. DeWille
1
1The Ohio State Biochemistry Program, Department of Veterinary Biosciences, The Ohio State University, 1925 Coffey Road, Columbus, OH 43210-1093, U.S.A.
1To whom correspondence should be addressed (email dewille.1@osu.edu).
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Publisher: Portland Press Ltd
Received:
January 15 2007
Revision Received:
March 08 2007
Accepted:
March 21 2007
Accepted Manuscript online:
March 21 2007
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2007 Biochemical Society
2007
Biochem J (2007) 405 (2): 341–349.
Article history
Received:
January 15 2007
Revision Received:
March 08 2007
Accepted:
March 21 2007
Accepted Manuscript online:
March 21 2007
Citation
Shanggen Zhou, James W. DeWille; Proteasome-mediated CCAAT/enhancer-binding protein δ (C/EBPδ) degradation is ubiquitin-independent. Biochem J 15 July 2007; 405 (2): 341–349. doi: https://doi.org/10.1042/BJ20070082
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