ABSTRACT
The nematode CED-4 protein and its human homolog Apaf-1 play a central role in apoptosis by functioning as direct activators of death-inducing caspases. A novel human CED-4/Apaf-1 family member called CARD4 was identified that has a domain structure strikingly similar to the cytoplasmic, receptor-like proteins that mediate disease resistance in plants. CARD4 interacted with the serine-threonine kinase RICK and potently induced NF-kappaB activity through TRAF-6 and NIK signaling molecules. In addition, coexpression of CARD4 augmented caspase-9-induced apoptosis. Thus, CARD4 coordinates downstream NF-kappaB and apoptotic signaling pathways and may be a component of the host innate immune response.
Subject(s)
Adaptor Proteins, Signal Transducing , Apoptosis , Caenorhabditis elegans Proteins , Calcium-Binding Proteins/metabolism , Carrier Proteins/metabolism , Helminth Proteins/metabolism , NF-kappa B/metabolism , Proteins/metabolism , Amino Acid Sequence , Apoptotic Protease-Activating Factor 1 , Base Sequence , Carrier Proteins/genetics , DNA, Complementary , Humans , Molecular Sequence Data , Nod1 Signaling Adaptor Protein , Sequence Homology, Amino Acid , Signal TransductionABSTRACT
Maturity-onset diabetes of the young 3 (MODY3) is a type of NIDDM caused by mutations in the transcription factor hepatocyte nuclear factor-1alpha (HNF-1alpha) located on chromosome 12q. We have identified four novel HNF-1alpha missense mutations in MODY3 families. In four additional and unrelated families, we observed an identical insertion mutation that had occurred in a polycytidine tract in exon 4. Among those families, one exhibited a de novo mutation at this location. We propose that instability of this sequence represents a general mutational mechanism in MODY3. We observed no HNF-1alpha mutations among 86 unrelated late-onset diabetic patients with relative insulin deficiency. Hence mutations in this gene appear to be most strongly associated with early-onset diabetes.
Subject(s)
Chromosomes, Human, Pair 12/genetics , DNA-Binding Proteins , Diabetes Mellitus, Type 2/genetics , Mutation/genetics , Nuclear Proteins/genetics , Transcription Factors/genetics , DNA Mutational Analysis , DNA Primers/chemistry , Family , Genetic Linkage , Haplotypes , Hepatocyte Nuclear Factor 1 , Hepatocyte Nuclear Factor 1-alpha , Hepatocyte Nuclear Factor 1-beta , Humans , Pedigree , Polymerase Chain Reaction , Polymorphism, Single-Stranded ConformationalABSTRACT
When testosterone concentrations in serum, saliva and seminal plasma were measured with a solid-phase enzymeimmunoassay in which antitestosterone antibody was bound to CNBr-Sepharose-4B, we found the ratios of testosterone in saliva and seminal plasma to that in serum were 2.5 +/- 0.2% and 5.19 +/- 0.42%. Testosterone level in saliva could be an index of free serum testosterone. In addition, we found a correlation between sperm motility and testosterone level in seminal plasma when sperm motility was measured with a transmembrane migration method. This enzymeimmunoassay could be applied to clinical studies of testosterone.
