Ubiquitin and the Biology of the Cell by Avram Hershko (auth.), Jan-Michael Peters, J. Robin Harris,

By Avram Hershko (auth.), Jan-Michael Peters, J. Robin Harris, Daniel Finley (eds.)

The final numerous years were a landmark interval within the ubiquitin box. The breadth of ubiquitin's roles in phone biology was once first sketched, and the significance of ubiquitin-dependent proteolysis as a regulatory mechanism won normal popularity. the various strands of labor that resulted in this new conception are re­ counted during this booklet. A final result of this development is that the sector has grown dramatically because the first ebook on ubiquitin was once released virtually a decade in the past [M. Rechsteiner (ed. ), Ubiquitin, Plenum Press, 1988]. during this span, scholars of the telephone cycle, transcription, sign transduction, protein sorting, neuropathology, melanoma, virology, and immunology have tried to chart the position of ubi surrender in of their specific experimental structures, and this integration of the sector into mobilephone biology as an entire keeps at a striking speed. we are hoping that for energetic researchers within the box in addition to for beginners and people at the fence, this publication will turn out worthy for its breadth, ancient point of view, and sensible assistance. Structural facts are actually on hand on a few of the elements of the ubiquitin pathway. The buildings have supplied simple insights into the weird biochemical mechanisms of ubiquitination and proteasome-mediated proteolysis. simply because high-speed special effects can show constructions extra successfully than print media, we now have supplemented the figures of the ebook with a global website that may exhibit the buildings in a versatile, viewer-controlled format.

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1988); (2) Hodgins et al. (1992); (3) Ecker et al. (1987); (4) Pickart et al. (1994); (5) Wilkinson et al. (1995); (6) Amason and Ellison (1994); (7) Pickart et al. (1992); (8) Spence et al. (1995); (9) Chau et al. (1989); (10) Finley et al. (1994); (II) Johnson et al. (1992); (12) Chau et al. (1989); (13) Baboshina and Haas (1996); (14) Burch and Haas (1994); (15) Beal et al. (1996); (16) Johnson et al. (1995). 32 • Cecile M. Pickart the structure and function of polyubiquitin chains are discussed further in Sections 3 and 4.

To date. the only well-characterized recogni- tion signal is the "N-end rule" (see Chapter 8). which. however. appears to have very limited cellular functions. The "destruction box" signal in mitotic cyclins and the cyclosome/ APC particle that acts on these proteins have been identified (see above). but it is not known whether a specific subunit of the cyclosome is responsible for the binding of the destruction box region. It also remains to be seen whether the phosphorylation of some proteins that is required for their ubiquitinylation (see above) is directly recognized by some E3 enzymes.

Certain mutations that provide insight into Table II Site-Specific Mutations in Ubiquitin Mutation G76A System/enzyme" Yeast Overexpressionlyeast Overexpressionlyeast Sole expressionlyeast Retic. fro II EI E3a, E2-25K Isopeptidase T L73Ll G75,7M Retic. fro II, E I Overexpressionlyeast Y59F Retic. fro II El E2-25K Phenotype/conclusionb In context of linear Vb fusion. inhibits processing proteases Slow growth Stress sensitivity; impaired proteolysis; isopeptidase inhibition Lethal Supports degradation at 10-25% wt rate Ternary complex destabilized: thiol ester but no adenylate Supports conjugation at -25% wt rate 10-fold inhibition for G76A as scissile bond; 100-fold inhibition for G76A at proximal chain terminus No activity Increased transcription of UB 14 polyubiquitin gene Supports degradation at 70-100% wt rate Properties in PPj-ATP exchange similar to wt Supports chain synthesis at 30% wt rate (V/K) References c 2 10 3,4 4 4 5 3 cited in 6 3 3 7 2.

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