Transcriptional regulation by histone ubiquitination and deubiquitination
- Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, North Carolina 27599, USA
This extract was created in the absence of an abstract.
Ubiquitin (Ub) is a 76-amino acid protein that is ubiquitously distributed and highly conserved throughout eukaryotic organisms. Whereas the extreme C-terminal four amino acids are in a random coil, its N-terminal 72 amino acids have a tightly folded globular structure (Vijay-Kumar et al. 1987; Fig. 1A). Since its discovery -28 years ago (Goldknopf et al. 1975), a variety of cellular processes including protein degradation, stress response, cell-cycle regulation, protein trafficking, endocytosis signaling, and transcriptional regulation have been linked to this molecule (Pickart 2001). Ubiquitylation is proposed to serve as a signaling module, and the information transmitted by this tag may depend on the nature of the modification, such as mono or poly-Ub, or the lysine residues on which the Ub attaches (Di Fiore et al. 2003).
(A) Proposed nucleosome structure with ubiquitinated histones. Modeled ubiquitin molecules (red) covalently attached to Lys 119 of histone H2A (cyan) and Lys 120 of histone H2B (gold) are shown as ribbon diagrams. For clarity, only one histone H2A and one H2B are shown in detail. The other H2A (green) and H2B (yellow) are shown in a surface representation together with H3 (pink) and H4 (light blue). The modeled isopeptide bond between the acceptor lysines and Gly 76 of ubiquitin are shown in a stick model (blue). The globular domain of histone H1 is shown in a green ribbon diagram. Location of Lys 36 and Lys 79 of H3 is indicated. The structure is modeled based on previous publications (Vijay-Kumar et al. 1987; Cerf et al. 1994; Goytisolo et al. 1996; Luger et al. 1997). Courtesy of Dr. Rui-Ming Xu. (B) Diagram depicting the differential effects of H2B ubiquitination and deubiquitination on H3-K4 and H3-K36 methylation. Enzymes (Rad6/Bre1, Ubp8, Set1, and Set2) that participate in this interplay are indicated.
Ub …
