GLI-similar (Glis) 1-3 proteins constitute a subfamily of the Krüppel-like zinc finger transcription factors that are closely related to the Gli family. They play key roles in the regulation of a number of physiological processes and have been implicated in several pathologies. Glis1-3 share a highly homologous zinc finger domain (ZFD) containing five Cys2-His2-type zinc finger (ZF) motifs with members of the Gli and Zic family [].Glis3 has repressor and activation functions []and is involved in pancreatic beta cell generation and insulin gene expression []. Glis3 deficient mice have decreased expression of several key transcription factors required for the endocrine development of the pancreas, such as Neurogenin3, NeuroD1, MafA and Pdx1 [, ]. Mutations in human glis3 cause a rare disease known as diabetes mellitus, neonatal, with congenital hypothyroidism (NDH) []. The glis3 gene has been identified as a susceptibility locus for the risk of type 1 and 2 diabetes [].
In prokaryotes and eukaryotes, pyruvate dehydrogenase complex (PDC) contains multiple copies of three enzymatic components: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2) and lipoamide dehydrogenase (E3) []. PDC catalyses the overall conversion of pyruvate to acetyl-CoA and CO2. In eukaryotes, PDC is located in the mitochondrial matrix [, ]. This entry represents agroup of E3-binding proteins, including dihydrolipoamide acetyltransferase (E2) and pyruvate dehydrogenase protein X component (known as Pdx1). Pdx1, found only in eukaryotes, plays a structural role in the complex by binding and positioning dihydrolipoamide dehydrogenase (E3) to the dihydrolipoamide acetyltransferase (E2) core []. Mutations in the Pdx1 gene has been linked to human disease [, ]. Mutations in the E2 gene cause pyruvate dehydrogenase deficiency [].
