Ubiquitin in protein

Vectorial Transport - A Function for Poly-Ubiquitination in Protein Dislocation ... 

In addition to protein proteolysis during mitosis, ubiquitin-mediated protein degradation ( ubiquitin/ proteasome) is also required at the G1 to S transition... 

As the ubiquitin proteasome pathway is a main route for protein clearance it is not surprising that in protein-opathies (disease caused by aggregate prone proteins) like sporadic Parkinson- or Huntington disease proteasome activity is reduced. Autosomal recessive loss of function of the E3 ligase parkin is the molecular base for one of the most common forms of familial Parkinson disease. 

Hoeller D, Hecker CM, Dikic I (2006) Ubiquitin and ubiquitin-like proteins in cancer pathogenesis. Nat Rev Cancer 6 776-788... 

Domain present in ubiquitin-regulatory proteins Uteroglobin... 

Alonso D. O. V. and Daggett V. Molecular dynamics simulations of protein unfolding and limited refolding characterization of partially unfolded states of ubiquitin in 60 % methanol and in water. J. Mol. Biol. (1995) 247 501-520. 

A. Hershko, H. Heller, E. Eytan, G. Kakklij, I. A. Rose, Role of the Alpha-Amino Group of Protein in Ubiquitin-Mediated Protein Breakdown , Proc. Natl. Acad. Sci. U.S.A. 1984, 81, 7021-025. 

Haas, A. L, Waems, J. V., Heeshko, A., and Rose, 1. A. Ubiquitin-activating enzyme. Mechanism and role in protein-ubiquitin conjugation, J Biol Chem 1982, 257, 2543-2548. 

Rao-Naik, C., delaCruz, W., Laplaza, J. M., Tan, S., Callis, J., and Fisher, A. J. The rub family of ubiquitin-like proteins. Crystal structure of Arabidopsis rubl and expression of multiple rubs in Arabidopsis, J Biol Chem 1998, 273, 34976-34982. 

From a chemical point of view, the El/ubiquitin thiol ester should be competent to donate ubiquitin to a substrate amino group. In fact, aminoacyl-errzyme thiol esters are used in exactly this way in non-ribosomal polypeptide synthesis, a process that was discovered around the same time as ubiquitin-protein conjugation [5]. In spite of the attractive simplicity of this model, however, biochemical reconstitution studies showed that besides El two additional fractions were required to conjugate ubiquitin to a model substrate. They were called ubiquitin carrier protein (E2) and ubiquitin-protein ligase (E3), respectively, since the respective factors seemed to act sequentially [6]. Interestingly, the E2 factor apparently formed a thiol ester with ubiquitin. Based on these results, Hershko and co-workers proposed the ubiquitin conjugation cascade (Figure 5.1). 

A., Carrano, a., Takizawa, C., Yamanaka, K., Pagano, M., Iwai, K., and CiECHANOVER, A. Identification of the ubiquitin carrier proteins, E2s, involved in signal-induced conjugation and subsequent degradation of IxrBa. 

Townsley, F. M., Aristarkhov, A., Beck, S., Hershko, A., and Ruderman, J. V. Dominant-negative cyclin-selective ubiquitin carrier protein E2-C/UbcH10 blocks cells in metaphase. Proc. Natl. Acad. Sei. USA 1997, 94, 2362-67. 

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