Glucocorticoids (GCs) are important regulators of skeletal muscle mass, and prolonged exposure will induce significant muscle atrophy. To better understand the mechanism of skeletal muscle atrophy induced by elevated GC levels, we examined three different models: exogenous synthetic GC treatment [dexamethasone (DEX)], nutritional deprivation, and denervation. Specifically, we tested the direct ...

IFN regulatory factor 7 (IRF7) is a potent transcription factor of type I IFNs and IFN-stimulated genes and is known as the master regulator of type I IFN-dependent immune responses. Because excessive responses could harm the host, IRF7 itself is delicately regulated at the transcriptional, translational, and posttranslational levels. Modification of IRF7 by small ubiquitin-related modifiers (S...

INTRODUCTION X-linked adrenal hypoplasia congenita (AHC) is a rare cause of adrenocortical insufficiency. Early postnatal diagnosis may prevent severe hypoglycemia, Addisonian crises and death. Low maternal estriol (E3) levels in the second trimester of pregnancy could indicate the possibility that the fetus suffers from a disorder that causes adrenal insufficiency. Suspicion is based on the fa...

It has been shown tha t d isubstituted butadiynes react with (Ph3P)2N i(C2H 4) [1] or (cod)2Ni [2] in the presence of Ph3P to yield m ononuclear complexes (Ph3P)2N i(//2( l :2 ) -R 'C = C C = C R ) (R ' = R = SiM e3 (1), 'B u (2) Ph (3) and R ' = 'Bu, R = SiMe3 (4) ör R ' = Ph, R = SiM e3 (5)) or dinuclear com plexes {(Ph3P)2Ni}2(//-? /2(l :2),^2(3 :4 ) -R 'C = C -C = C R ) (R ' = R = SiM e3 (6...

Nedd4 E3 ligases are members of the HECT E3 ubiquitin ligase family and regulate ubiquitination-mediated protein degradation. In this report, we demonstrate that calcium releases the C2 domain-mediated auto-inhibition in both Nedd4-1 and Nedd4-2. Calcium disrupts binding of the C2 domain to the HECT domain. Consistent with this, calcium activates the E3 ubiquitin ligase activity of Nedd4. Eleva...

The histamine H2-receptor antagonists have been identified as inhibitors of human liver aldehyde dehydrogenase (EC 1.2.1.3) isozymes, E1, E2, and E3. Inhibition was strongest with the E3 isozyme, whose substrates include gamma-aminobutyraldehyde, the aldehyde metabolites of polyamines, and betaine aldehyde. Burimamide, metiamide, cimetidine guanidine, cimetidine, and tiotidine were competitive ...

Protein ubiquitination regulates numerous cellular functions in eukaryotes. The prevailing view about the role of RING or U-box ubiquitin ligases (E3) is to provide precise positioning between the attached substrate and the ubiquitin-conjugating enzyme (E2). However, the mechanism of ubiquitin transfer remains obscure. Using the carboxyl terminus of Hsc70-interacting protein as a model E3, we s...

The RBR (RING-BetweenRING-RING) or TRIAD [two RING fingers and a DRIL (double RING finger linked)] E3 ubiquitin ligases comprise a group of 12 complex multidomain enzymes. This unique family of E3 ligases includes parkin, whose dysfunction is linked to the pathogenesis of early-onset Parkinson's disease, and HOIP (HOIL-1-interacting protein) and HOIL-1 (haem-oxidized IRP2 ubiquitin ligase 1), m...

Genes in the early region 3 (E3) of the adenovirus genome allow the virus to evade host immune responses by interfering with major histocompatibility (MHC) class I-mediated antigen presentation and tumor necrosis factor-alpha (TNF-alpha)- or Fas-induced apoptosis of infected cells. Autoimmune type 1 diabetes (T1D) is inhibited in NOD mice transgenically expressing all E3 genes under control of ...

This study examined apolipoprotein (apo) B metabolism in normolipemic subjects homozygous for the apo E2 (n = 4), apo E3 (n = 5), or apo E4 (n = 5) phenotype. Radioiodinated very low density lipoprotein (VLDL1) (ultracentrifuge flotation rate [Sf] 60-400) and VLDL2 (Sf 20-60) were injected into volunteers and the conversion of apo B was followed through intermediate density lipoprotein (IDL) to...