Ubiquitin-conjugating enzymes

Ubiquitin tags proteins for protein degradation. The ubiquitination requires three different enzymatic activities, a ubiquitin-activating enzyme (El), a ubiquitin-conjugating enzyme (E2 or Ubc) and a ubiquitin ligase (E3). The action of all three enzymes leads to the establishment of a poly-ubiquitin chain on target proteins which are then recognized and proteolyzed by the 26S proteasome. 

Robust decreases in the expression of the various proteasome subunits and ubiquitin-conjugating enzymes have been described in prefrontal cortex in schizophrenia. Neuronal ubiquitin and proteasomes play an important role in the assembly, function and plasticity of the synapse. Structural proteins including tubulin and a-spectrin also show decreased expression in prefrontal cortex. 

Ubiquitin-conjugating enzyme E2, catalytic domain homologs... 

Deng, L, Wang, C., Spencer, E., Yang, L, Braun, A., You, f., Slaughter, C., Pickart, C., and Chen, Z. J. Activation of the IkappaB kinase complex by TRAE6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain, Cdl 2000, 103, 351—361. 

Loeick, K. L., et al., RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination. Proc Natl Acad Sci USA, 1999, 96(20), 11364-9. 

Moynihan, T. P., et al., The ubiquitin-conjugating enzymes UbcH7 and UbcH8 interact with RING finger/IBR motif-containing domains of HHARI and H7-AP1./... 

Lisztwan, j., et al., Association of human CUL-1 and ubiquitin-conjugating enzyme CDC34 with the F-box protein p45(SKP2) evidence for evolutionary conservation in the subunit composition of the CDC34-SCF pathway. Embo J, 1998, 37/2/, 368-83. 

Hofmann, R. M. and C. M. Pickart, Noncanonical MMS2-encoded ubiquitin-conjugating enzyme functions in assembly of novel polyubiquitin chains for DNA repair. Cell, 1999, 96(5), 645-53. 

Ulrich, H. D. and S. Jentsch, Two Ring-finger proteins mediate cooperation between ubiquitin-conjugating enzymes in DNA repair. EmboJ, 2000, 19(13), 3388-97. 

Ardley, H. C., et al., Features of the parkin/ariadne-like ubiquitin ligase, HHARI, that regulate its interaction with the ubiquitin-conjugating enzyme, Ubch7. / Biol Chem, 2001, 276(22), 19640-7. 

Ito, K., et al., N-Terminally extended human ubiquitin-conjugating enzymes (E2s) mediate the ubiqui-tination of RING finger proteins, ARA54 and RNE8. Eur J Biochem,... 

Fig. 5.1. The ubiquitin-conjugation pathway. Steps in ubiquitin activation and substrate modification. El, ubiquitin activating enzyme E2, ubiquitin-conjugating enzyme E3, ubiquitin-protein ligase. Atoms involved in the thiol ester and amide bonds are shown.

The functional range of the ubiquitin-conjugating enzyme family is easily appreciated by considering the family members in a single organism. Table 5.1 summa-... 

Jentsch, S., McGrath, J. P., and Varshavsky, A. The yeast DNA repair gene RAD6 encodes a ubiquitin-conjugating enzyme. Nature 1987, 329, 131-34. 

Baneejee, a., Deshaies, R. J., and Chau, V. Characterization of a dominant negative mutant of the cell cycle ubiquitin-conjugating enzyme Cdc34. J. Biol. Chem. 1995, 270, 26209-15. 

T., Cummings, M., and Ellison, M. J. The tail of a ubiquitin-conjugating enzyme redirects multi-ubiquitin chain synthesis from the lysine 48-... 

Cook, W. J., Jeffrey, L. C., Sullivan, M. L, and Vierstra, R. D. Three-dimensional structure of a ubiquitin-conjugating enzyme (E2)./. Biol. 

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