scholarly journals Diffuse Glomerular Nodular Lesions in Diabetic Pigs Carrying a Dominant-Negative Mutant Hepatocyte Nuclear Factor 1-Alpha, an Inheritant Diabetic Gene in Humans

PLoS ONE ◽  
2014 ◽  
Vol 9 (3) ◽  
pp. e92219 ◽  
Author(s):  
Satoshi Hara ◽  
Kazuhiro Umeyama ◽  
Takashi Yokoo ◽  
Hiroshi Nagashima ◽  
Michio Nagata
Keyword(s):  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Nodular Lesions ◽  
Nuclear Factor 1 ◽  
Negative Mutant

Dominant-negative mutant hepatocyte nuclear factor 1α induces diabetes in transgenic-cloned pigs

2009 ◽  
Vol 18 (5) ◽  
pp. 697-706 ◽  
Author(s):  
Kazuhiro Umeyama ◽  
Masahito Watanabe ◽  
Hitoshi Saito ◽  
Mayuko Kurome ◽  
Sadaaki Tohi ◽  
...  
Keyword(s):  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Hepatocyte Nuclear Factor 1Α ◽  
Negative Mutant

Mutation P291fsinsC in the Transcription Factor Hepatocyte Nuclear Factor-1  is Dominant Negative

Diabetes ◽  
1998 ◽  
Vol 47 (8) ◽  
pp. 1231-1235 ◽  
Author(s):  
K. Yamagata ◽  
Q. Yang ◽  
K. Yamamoto ◽  
H. Iwahashi ◽  
J.-i. Miyagawa ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Dominant Negative ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Nuclear Factor 1

scholarly journals Zyxin regulates migration of renal epithelial cells through activation of hepatocyte nuclear factor-1β

2013 ◽  
Vol 305 (1) ◽  
pp. F100-F110 ◽  
Author(s):  
Yun-Hee Choi ◽  
Brian T. McNally ◽  
Peter Igarashi
Keyword(s):  
Transcription Factor ◽  
Epithelial Cells ◽  
Nuclear Translocation ◽  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Epithelial Tissue ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Lim Domain ◽  
Renal Epithelial Cells

Hepatocyte nuclear factor-1β (HNF-1β) is an epithelial tissue-specific transcription factor that regulates gene expression in the kidney, liver, pancreas, intestine, and other organs. Mutations of HNF-1β in humans produce renal cysts and congenital kidney anomalies. Here, we identify the LIM-domain protein zyxin as a novel binding partner of HNF-1β in renal epithelial cells. Zyxin shuttles to the nucleus where it colocalizes with HNF-1β. Immunoprecipitation of zyxin in leptomycin B-treated cells results in coprecipitation of HNF-1β. The protein interaction requires the second LIM domain of zyxin and two distinct domains of HNF-1β. Overexpression of zyxin stimulates the transcriptional activity of HNF-1β, whereas small interfering RNA silencing of zyxin inhibits HNF-1β-dependent transcription. Epidermal growth factor (EGF) induces translocation of zyxin into the nucleus and stimulates HNF-1β-dependent promoter activity. The EGF-mediated nuclear translocation of zyxin requires activation of Akt. Expression of dominant-negative mutant HNF-1β, knockdown of zyxin, or inhibition of Akt inhibits EGF-stimulated cell migration. These findings reveal a novel pathway by which extracellular signals are transmitted to the nucleus to regulate the activity of a transcription factor that is essential for renal epithelial differentiation.

Regulation of kidney-specific Ksp-cadherin gene promoter by hepatocyte nuclear factor-1β

2002 ◽  
Vol 283 (4) ◽  
pp. F839-F851 ◽  
Author(s):  
Yun Bai ◽  
Marco Pontoglio ◽  
Thomas Hiesberger ◽  
Angus M. Sinclair ◽  
Peter Igarashi
Keyword(s):  
Promoter Activity ◽  
Gene Promoter ◽  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Specific Gene ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Tissue Specific ◽  
Transfected Cells

Kidney-specific cadherin (Ksp-cadherin) is a tissue-specific member of the cadherin family that is expressed exclusively in the kidney and developing genitourinary tract. Recent studies have shown that the proximal 250 bp of the Ksp-cadherin gene promoter are sufficient to direct tissue-specific gene expression in vivo and in vitro. The proximal 120 bp of the promoter are evolutionarily conserved between mouse and human and contain a DNase I hypersensitive site that is kidney cell specific. At position −55, the promoter contains a consensus recognition site for hepatocyte nuclear factor-1 (HNF-1). Mutations of the consensus HNF-1 site and downstream GC-boxes inhibit promoter activity in transfected cells. HNF-1α and HNF-1β bind specifically to the −55 site, and both proteins transactivate the promoter directly. Expression of Ksp-cadherin is not altered in the kidneys of HNF-1α-deficient mice. However, expression of a gain-of-function HNF-1β mutant stimulates Ksp-cadherin promoter activity in transfected cells, whereas expression of a dominant-negative mutant inhibits activity. These studies identify Ksp-cadherin as the first kidney-specific promoter that has been shown to be regulated by HNF-1β. Mutations of HNF-1β, as occur in humans with inherited renal cysts and diabetes, may cause dysregulated Ksp-cadherin promoter activity.

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