Ubiquitination

Di stefano D L and Wand A J 1987 Two-dimensional NMR study of human ubiquitin a main chain directed assignment and structure analysis Biochemistry 26 7272-81... 

Weber P L, Brown S 0 and Mueller L 1987 Sequential NMR assignment and secondary structure identification of human ubiquitin Biochemistry 26 7282-90... 

Schneider D M, Deliwo M J and Wand A J 1992 Fast internal main-chain dynamics of human ubiquitin Biochemistry 31 3645-52... 

Toyopearl HW-50S resin has been used to help isolate the ubiquitin-histone conjugate mH2A from the unicellular ciliated protozoan Tetrahymena pyriformis. Figure 4.49 shows the separation of mH2A from the histone, H2A. The sole difference between these two components is a small polypeptide, ubiquitin (approximately 8500 Da). The mH2A fraction was then further purified by HPLC on a Tosoh ODS-silica column (52). One of the many benefits... 

FIGURE 4.49 Isolation of a complex protein conjugate on Toyopearl HW-50S. Column 22 mm X 83 cm. Sample Fraction from crude Tetrahymena H2A containing the ubiquitin-histone conjugate uH2A. Elution 10 nM HCI. Flow rate 0.1 ml/min. Detection UV at 230 nm. 

Adaptor Proteins. Figure 1 Adaptor protein domains. A scheme of the domain structures of some well-characterized adaptor proteins is shown. Descriptions of domain characteristics are in main text except C2, binds to phospholipids GTPase activating protein (GAP) domain, inactivates small GTPases such as Ras Hect domain, enzymatic domain of ubiquitin ligases and GUK domain, guanylate kinase domain. For clarity, not all domains contained within these proteins are shown. 

WW domains (named after the one letter abbreviation for the amino acid tryptophan) are small regions of around 30 residues, which, like SH3 domains, bind to polyproline sequences. These sequences often contain the consensus sequence PPXY or PPLP. Examples of proteins that contain WW domains include Nedd4 E3 ubiquitin ligase (Fig. 1) and IQGAP1. 

Emerging evidence suggests that dysfunction of the ubiquitin-proteasome system may be part of the pathophysiology of sporadic Parkinson s disease, especially... 

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

Chromatin is composed of nucleosomes, where each comprise 147 base pairs of DNA wrapped around an octamer oftwo copies of each histone H2A, H2B, H3, and H4. Nucleosomes are folded into higher-order structures that are stabilized by linker histones. Chromatin structure can be altered by enzymes that posttranslationally modify histones (e.g., through phosphorylation, acetylation, methylation, or ubiquitination) or by ATP-driven chromatin-remodeling complexes that alter nucleosome position and/or composition. 

The human genome contains more than 90 different DUBs. Besides cleaving ubiquitin from distinct substrates, DUBs are also responsible for the recycling of free ubiquitin from ubiquitin chains and processing of ubiquitin- or ubiquitin like precursor proteins. Certain DUBs are also associated with the proteasome in order to detach ubiquitin chains before proteolysis. 

Transforming Growth Factor-Beta Ubiquitin/Proteasome... 

The N-end rule relates the in vivo half-life of a protein to the identity of its N-terminal residue. Proteins with destabilizing N-terminal residues such as arginine and leucine are recognized by a RING-type ubiquitin ligase (termed N-recognin or E3-a) that, together with a specific ubiquitin c, mediates poly-ubiquitylation. 

F-adjacent Transcript-10 (FAT 10) is composed of two ubiquitin-like domains and capable to mark conjugated proteins for proteasomal degradation independent of ubiquitin. FAT10 is inducible by IFN-y and TNF and induces apoptosis when over expressed. 

Fujita Y, Krause G, Scheffner M et al (2002) Hakai, a c-Cbl-like protein, ubiquitinates and induces endo-cytosis of the E-cadherin complex. Nat Cell Biol 4(3) 222-231... 

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