title: The tribbles gene family and lipoprotein metabolism.
abstract: OBJECTIVE
  The success of high throughput sequencing programmes, including the Human Genome Project led to the 'identification' of a large number of novel genes of completely unknown function. Since then, many of these genes have been subject to functional studies focussed on uncovering their biological importance. Recent advances in genome-wide screening of DNA sequence variants as well as focussed genetic studies identified a number of candidate loci contributing to the development of complex diseases, including those affecting lipid homeostasis. An excellent example for the convergence of genetics and experimental biology is the tribbles gene family which was among those identified both in recent genetic studies and were implicated in dysregulation of lipid levels experimentally. Thus, there is a need now to take a step back and reconcile these findings accumulated over recent years.
  
  
  RESULTS
  Allelic variants of tribbles proteins have been associated with the control of fatty acid synthesis and insulin resistance as well as regulating plasma triglyceride and HDL cholesterol levels. Several mechanisms of molecular action have been proposed for the tribbles mediated control of these processes, including the regulation of signalling events, protein turnover and transcription, sometimes with conflicting evidence emerging.
  
  
  CONCLUSIONS
  This review attempts to synthesize knowledge obtained on the biology of the tribbles protein family in the context of lipid metabolism as well as discussing the recently emerging genetic evidence for the importance of these proteins in human disease.
authors.affiliation: Department of Cardiovascular Science, University of Sheffield, Sheffield, UK.
authors.forename: Adrienn
authors.initials: A
authors.lastname: Angyal
authors.forename: Endre
authors.initials: E
authors.lastname: Kiss-Toth
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D050356:Lipid Metabolism / Q000235:genetics*; D008074:Lipoproteins / Q000378:metabolism*; D024821:Metabolic Syndrome / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008074:Lipoproteins; D012097:Repressor Proteins; C493170:TRIB1 protein, human; C474831:TRIB3 protein, human; D014280:Triglycerides; D017346:Protein Serine-Threonine Kinases