Characterization of a Cofactor That Regulates Dimerization of a Mammalian Homeodomain Protein

Abstract

Dimerization among transcription factors has become a recurrent theme in the regulation of eukaryotic gene expression. Hepatocyte nuclear factor-1 alpha (HNF-1 alpha) is a homeodomain-containing protein that functions as a dimer. A dimerization cofactor of HNF-1 alpha (DCoH) was identified that displayed a restricted tissue distribution and did not bind to DNA, but, rather, selectively stabilized HNF-1 alpha dimers. The formation of a stable tetrameric DCoH-HNF-1 alpha complex, which required the dimerization domain of HNF-1 alpha, did not change the DNA binding characteristics of HNF-1 alpha, but enhanced its transcriptional activity. However, DCoH did not confer transcriptional activation to the GAL4 DNA binding domain. These results indicate that DCoH regulates formation of transcriptionally active tetrameric complexes and may contribute to the developmental specificity of the complex.

Quantitative proteomic analysis of S-nitrosated proteins in diabetic mouse liver with ICAT switch method

“…S-nitrosated ArgBP2 was only detected in KK-Ay mouse liver, suggesting that Snitrosation of this protein may contribute to dysfunction of the glucose transport pathway. (B) Hepatocyte pterin 4 alpha carbinolamine dehydratase/dimerization cofactor (PCBD1), also known as dimerizing cofactor for HNF1 (DCoH), can bind to the HNF1 family of transcriptional activators, nuclear factor 1 alpha (TCF1) 1 (Mendel et al, 1991). The HNF1-DCoH complex regulates the expression of a large group of genes related to metabolism and the insulin pathway in liver.…”

Human Pterin‐4α‐Carbinolamine Dehydratase/Dimerization Cofactor of Hepatocyte Nuclear Factor‐1α

“…A major question, which has been the subject of some debate, is the state of oligomerization of PCD both in its function as a dehydratase, and also regarding its mode of interaction with HNF-la. The dimerization cofactor of HNF-la has been reported to be a dimer [39] ; PCD, on the other hand, crystallizes as a tetramer, or, better, as a dimer of dimers [17]. A tetramer is consistent with the results of our gel filtration experiments performed in the presence and absence of q-6,6-Me2-H,pterin, which is one of the best ligands studied, and of the PAGE experiments under non-denaturing conditions [38] (and this work).…”

MLL-mediated transcriptional gene regulation investigated by gene expression profiling

“…The dimerization cofactor of hepatocyte nuclear factor 1 alpha, the bifunctional DCoH protein, stabilizes HNF-1 alpha dimers and enhances their transcriptional activity (Mendel et al, 1991). In addition, DCoH protein is a pterin-4-a-carbinolamine dehydratase that is involved in the regeneration of the cofactor tetrahydrobiopterin.…”