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Ubiquitination of receptor protein-tyrosine kinases (RPTKs) terminates signaling by marking active receptors for degradation. c-Cbl, an adapter protein for RPTKs, positively regulates RPTK ubiquitination in a manner dependent on its variant SRC homology 2 (SH2) and RING finger domains. Ubiquitin-protein ligases (or E3s) are the components of ubiquitination(More)
Glucocorticoids are essential for the increase in protein breakdown in skeletal muscle normally seen during fasting. To determine which proteolytic pathway(s) are activated upon fasting, leg muscles from fed and fasted normal rats were incubated under conditions that block or activate different proteolytic systems. After food deprivation (1 day), the(More)
Most of the increased protein degradation in muscle atrophy caused by starvation and denervation is due to activation of a non-lysosomal ATP-dependent proteolytic process. To determine whether expression of the ubiquitin-proteasome-dependent pathway is activated in atrophying muscles, we measured the levels of mRNA for ubiquitin (Ub) and proteasome(More)
Upon fasting, an increase in proteolysis occurs in rat skeletal muscle and is associated with increased levels of ubiquitin-protein conjugates. As this suggests that formation of conjugates may be activated upon fasting, we studied the expression of the gene encoding the 14-kDa ubiquitin-conjugating enzyme (E2(14k)). A cDNA encoding rat E2(14k) was isolated(More)
A genome wide search for new BH3-containing Bcl-2 family members was conducted using position weight matrices (PWM) and identified a large (480kDa), novel BH3-only protein, originally called LASU1 (now also known as Ureb-1, E3(histone), ARF-BP1, and Mule). We demonstrated that LASU1 is an E3 ligase that ubiquitinated Mcl-1 in vitro and was required for its(More)
In response to serum withdrawal, when overall rates of proteolysis increase in cultured fibroblasts, proteins containing peptide regions similar to Lys-Phe-Gln-Arg-Gln (KFERQ) are targeted to lysosomes for degradation, and the intracellular concentrations of these proteins decline [Chiang & Dice (1988) J. Biol. Chem. 263, 6797-6805]. To test whether such(More)
  • Simon Wing
  • The international journal of biochemistry & cell…
  • 2003
Ubiquitination of proteins is now recognized to target proteins for degradation by the proteasome and for internalization into the lysosomal system, as well as to modify functions of some target proteins. Although much progress has been made in characterizing enzymes that link ubiquitin to proteins, our understanding of deubiquitinating enzymes is less(More)
The rapid atrophy of skeletal muscles upon fasting or denervation is due largely to an increased rate of protein breakdown. Blocking the lysosomal or the Ca(2+)-dependent pathways did not prevent increased proteolysis in muscles from fasted animals or following denervation. In contrast, upon food deprivation, the nonlysosomal ATP-dependent process increased(More)
During spermatogenesis, a large fraction of cellular proteins is degraded as the spermatids evolve to their elongated mature forms. In particular, histones must be degraded in early elongating spermatids to permit chromatin condensation. Our laboratory previously demonstrated the activation of ubiquitin conjugation during spermatogenesis. This activation is(More)
The Saccharomyces cerevisiae ubiquitin-conjugating enzymes (E2s) UBC4 and UBC5 are essential for degradation of short-lived and abnormal proteins. We previously identified rat cDNAs encoding two E2s with strong sequence similarity to UBC4 and UBC5. These E2 isoforms are widely expressed in rat tissues, consistent with a fundamental cellular function for(More)