Ubiquitin-mediated proteolysis

Baldi, L., Brown, K., Feanzoso, G. and Siebenlist, U. Critical role for lysines 21 and 22 in signal-induced, ubiquitin-mediated proteolysis of I kappa B-alpha. J Biol Chem 1996, 271, 376-9. 

Bashir, T. and Pagano, M. Aberrant ubiquitin-mediated proteolysis of cell cycle regulatory proteins and oncogenesis. Adv Cancer Res 2003, 88, 101-44. 

Deveraux, Q., van Nogker, S., Mahaeeey, D., Vierstra, R., and Rechsteiner, M. Inhibition of ubiquitin-mediated proteolysis by the Arabidopsis 26 S protease subunit S5a. J. Biol. Chem. 1995, 29660-29663. 

Salghetti, S. E., Muratani, M., WijNEN, H., Futgher, B., and Tansey, W. P. Functional overlap of sequences that activate transcription and signal ubiquitin-mediated proteolysis. Proc. Natl. Acad. Sci. 

Another speculation has been put forth. Because the turnover of methyl groups such as the modification on lysine residues is low, ubiquitination of histone N-termini might serve as a signal for proteolysis of methylated histones such that dynamic regulation of the chromatin is possible. Since no histone demethylases have been identified, ubiquitin-mediated proteolysis might be a way to reverse the effects of histone methylation. ... 

Phosphorylation-Dependent Substrate Recognition in Ubiquitin-Mediated Proteolysis... 

Figure 4. Ubiquitin-mediated proteolysis regulates the onset and demise of Cdk activity during the cell division cycle. The Anaphase Promoting Complex/Cyclosome (APC/C) is active from the onset of anaphase until the end of G1 phase, during which it targets mitotic cyclins (Clbs) and other proteins such as Pdsl. The SCF complex is constitutively active but only targets Sicl and other substrates once they have been specifically phosphorylated by G1 cyclin (Cln)-Cdk (Cdc28) activity. See text for details.

Ciechanover, A., Orian, A., and Schwartz, A.L. (2000). Ubiquitin-mediated proteolysis Biological regulation via destruction. BioEssays 22,442-451. 

Helenius A (1994) How N-linked oligosaccharides affect glycoprotein folding in the endoplasmic reticulum. Mol Biol Cell 5 253-265 Hershko A (1997) Roles of ubiquitin-mediated proteolysis in cell cyde control. Curr Opin Cell Biol 9 788-99... 

The inhibitor p27 is regulated at the post-translational level. p27 4 exists in an inactive, masked form in proliferating cells. It may be converted into the active form by an as yet unknown mechanism so that the cell cycle can be halted. Activation of p27 may be triggered by treatment of cells with TGPp, by cell-cell contact and by an increase in the cAMP concentration. Purthermore, p27 is subject to specific, ubiquitin-mediated proteolysis (see below). 

Ryo, A., Suizu, F., Yoshida, Y., Perrem, K., Liou, Y.C., Wulf, G., Rottapel, R., et al. Regulation of NF-kappaB signaling by Pin 1-dependent prolyl isomerization and ubiquitin-mediated proteolysis of p65/RelA. Mol Cell 12 (2003) 1413-1426. 

Doss-Pepe, E.W., Stenroos, E.S., Johnson, W.G. and Madura, K. (2003) Ataxin-3 interactions with rad23 and valosin-containing protein and its associations with ubiquitin chains and the proteasome are consistent with a role in ubiquitin-mediated proteolysis. Mol. Cell Biol. 28, 6469-6483. 

Wojcik et al., Ubiquitin-mediated proteolysis centers in HeLa cells. Indication from studies of an inhibitor of the chymotrypsin-like activity of the proteasome, Eur. J. Cell BioL 71 (19%) 311-318. 

HPV-16 encodes a set of early gene oncoproteins (E6 and E7) responsible for cellular immortalization. HPV types 16 and 18 E6 and E7 proteins are known to interact strongly with p53 and retinoblastoma (Rb) tumor suppressor gene products, respectively (2). The association of E6 with p53 marks this tumor suppressor for rapid ubiquitin-mediated proteolysis. Reduced levels of p53 prevent the cell from activating cell cycle arrest and/or induction of apoptosis in genetically mutated cells. 

Fig. 2.16 Regu lation and proteolysis of the transcription factor NFkB. The Ubiquitin-protea-some pathway is involved in the regulation of NFkB in two ways. The 50 kDa subunit of NFkB is formed from a 105 kDa precursor via ubiquitin mediated proteolysis. In the cytosol NFkB is heterodimeric and inactive, bound to the inhibitor protein IkB.

Most cyclins are the target of ubiquitin-mediated proteolysis, and this degradation is a major mechanism for reducing cyclin concentrations at distinct cell cycle stages. 

A major control of the level of p27KIP1 is exerted by ubiquitin-mediated proteolysis, which has been shown to be dependent on phosphorylation of p27KIP1 by cyclin E-CDK2 complexes (see Section 13.3.1). 

Yew, P.R. (2001) Ubiquitin-mediated proteolysis of vertebrate Gl- and S-phase regulators. J.Cell Physiol, 187, 1-10. 

Ubiquitin-mediated proteolysis El (UBA), E2 (UBC), E3 (UBR), F-Box proteins, SKPl, cdc34, APC, cdc4, Grrl, VHL, Cul2, Rbxl Von Hippel—Lindau, Cancer, Parkinsoifs... 

In these hypercatabolic states, skeletal muscle protein synthesis decreases, and protein degradation increases. Oxidation of BCAA is increased and glutamine production enhanced. Amino acid uptake is diminished. Cortisol is the major hormonal mediator of these responses, although certain cytokines may also have direct effects on skeletal muscle metabohsm. As occurs during fasting and metabolic acidosis, increased levels of cortisol stimulate ubiquitin-mediated proteolysis, induce the synthesis of glutamine synthetase, and enhance release of amino acids and glutamine from the muscle cells. 

Gaczynska M, Rock KL, Goldberg AL (1993) y-Interferon and expression of MHC genes regulate peptide hydrolysis by proteasomes. Nature 365 264-267 Ghislain M, Dohmen RJ, Levy F, Varshavsky A (1996) Cdc48p interacts with Ufd3p, a WD repeat protein required for ubiquitin-mediated proteolysis in Saccharomyces cerevisiae. EMBO J 15 4884-4899... 

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