scholarly journals Hepatocyte nuclear factor 1 beta: A perspective in cancer

2021 ◽  
Author(s):  
Shubhra Chandra ◽  
Srilakshmi Srinivasan ◽  
Jyotsna Batra
Keyword(s):  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Nuclear Factor 1

The human beta fibrinogen promoter contains a hepatocyte nuclear factor 1-dependent interleukin-6-responsive element

1993 ◽  
Vol 13 (2) ◽  
pp. 1183-1193
Author(s):  
J Dalmon ◽  
M Laurent ◽  
G Courtois
Keyword(s):  
Binding Site ◽  
Acute Phase ◽  
Interleukin 6 ◽  
Constitutive Expression ◽  
Nuclear Proteins ◽  
Functional Coupling ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Tissue Specific ◽  
Nuclear Factor 1

Acute-phase reactants are liver proteins whose synthesis is positively or negatively regulated during inflammation. The main mediators of this phenomenon are glucocorticoids and interleukin-6 (IL-6), a pleiotropic cytokine that also controls hematopoiesis. Functional analysis of several acute-phase reactant promoter regions has identified two major DNA motifs used by IL-6-regulated genes. The first one corresponds to a CTGG(G/A)AA sequence, and the other is a binding site for members of the C/EBP family of nuclear proteins. We have previously shown that the human beta fibrinogen (beta Fg) promoter contains an IL-6-responsive region, located between bp -150 and -67 (P. Huber, M. Laurent, and J. Dalmon, J. Biol. Chem. 265:5695-5701, 1990). In this study, using DNase I footprinting, mobility shift assays, and mutagenesis, we demonstrate that at least three subdomains of this region are necessary to observe a full response to IL-6. The most distal contains a CTGGGAA motif, and its mutation inhibits IL-6 stimulation. Another, which is able to interact with several distinct nuclear proteins, among them members of the C/EBP family, is dispensable for IL-6 induction but plays an important role in the constitutive expression of beta Fg. Finally, a proximal hepatocyte nuclear factor 1 binding site, already described as the major determinant of beta Fg tissue-specific expression, is also required for IL-6 stimulation. These results indicate a complex interplay between nuclear proteins within the beta Fg IL-6-responsive region and suggest a tight functional coupling between the tissue-specific and inducible elements.

scholarly journals Hepatitis C Virus Infection Suppresses GLUT2 Gene Expression via Downregulation of Hepatocyte Nuclear Factor 1 

2012 ◽  
Vol 86 (23) ◽  
pp. 12903-12911 ◽  
Author(s):  
C. Matsui ◽  
I. Shoji ◽  
S. Kaneda ◽  
I. R. Sianipar ◽  
L. Deng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Infection ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Hepatitis C Virus Infection ◽  
Glut2 Gene ◽  
Nuclear Factor 1

scholarly journals Clinical Application of 1,5-Anhydroglucitol Measurements in Patients with Hepatocyte Nuclear Factor-1  Maturity-Onset Diabetes of the Young

Diabetes Care ◽  
2008 ◽  
Vol 31 (8) ◽  
pp. 1496-1501 ◽  
Author(s):  
J. Skupien ◽  
S. Gorczynska-Kosiorz ◽  
T. Klupa ◽  
K. Wanic ◽  
E. A. Button ◽  
...  
Keyword(s):  
Clinical Application ◽  
Nuclear Factor ◽  
Maturity Onset Diabetes ◽  
Hepatocyte Nuclear Factor ◽  
Onset Diabetes ◽  
Nuclear Factor 1

scholarly journals Hepatitis C Virus NS5A Protein Promotes the Lysosomal Degradation of Hepatocyte Nuclear Factor 1α via Chaperone-Mediated Autophagy

2018 ◽  
Vol 92 (13) ◽  
Author(s):  
Chieko Matsui ◽  
Lin Deng ◽  
Nanae Minami ◽  
Takayuki Abe ◽  
Kazuhiko Koike ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Lysosomal Degradation ◽  
Selective Degradation ◽  
Ns5a Protein ◽  
Infected Cells ◽  
Nuclear Factor 1 ◽  
Chaperone Mediated Autophagy

ABSTRACT Hepatitis C virus (HCV) infection is closely associated with type 2 diabetes. We reported that HCV infection induces the lysosomal degradation of hepatocyte nuclear factor 1 alpha (HNF-1α) via interaction with HCV nonstructural protein 5A (NS5A) protein, thereby suppressing GLUT2 gene expression. The molecular mechanisms of selective degradation of HNF-1α caused by NS5A are largely unknown. Chaperone-mediated autophagy (CMA) is a selective lysosomal degradation pathway. Here, we investigated whether CMA is involved in the selective degradation of HNF-1α in HCV-infected cells and observed that the pentapeptide spanning from amino acid (aa) 130 to aa 134 of HNF-1α matches the rule for the CMA-targeting motif, also known as KFERQ motif. A cytosolic chaperone protein, heat shock cognate protein of 70 kDa (HSC70), and a lysosomal membrane protein, lysosome-associated membrane protein type 2A (LAMP-2A), are key components of CMA. Immunoprecipitation analysis revealed that HNF-1α was coimmunoprecipitated with HSC70, whereas the Q130A mutation (mutation of Q to A at position 130) of HNF-1α disrupted the interaction with HSC70, indicating that the CMA-targeting motif of HNF-1α is important for the association with HSC70. Immunoprecipitation analysis revealed that increasing amounts of NS5A enhanced the association of HNF-1α with HSC70. To determine whether LAMP-2A plays a role in the degradation of HNF-1α protein, we knocked down LAMP-2A mRNA by RNA interference; this knockdown by small interfering RNA (siRNA) recovered the level of HNF-1α protein in HCV J6/JFH1-infected cells. This result suggests that LAMP-2A is required for the degradation of HNF-1α. Immunofluorescence study revealed colocalization of NS5A and HNF-1α in the lysosome. Based on our findings, we propose that HCV NS5A interacts with HSC70 and recruits HSC70 to HNF-1α, thereby promoting the lysosomal degradation of HNF-1α via CMA. IMPORTANCE Many viruses use a protein degradation system, such as the ubiquitin-proteasome pathway or the autophagy pathway, for facilitating viral propagation and viral pathogenesis. We investigated the mechanistic details of the selective lysosomal degradation of hepatocyte nuclear factor 1 alpha (HNF-1α) induced by hepatitis C virus (HCV) NS5A protein. Using site-directed mutagenesis, we demonstrated that HNF-1α contains a pentapeptide chaperone-mediated autophagy (CMA)-targeting motif within the POU-specific domain of HNF-1α. The CMA-targeting motif is important for the association with HSC70. LAMP-2A is required for degradation of HNF-1α caused by NS5A. We propose that HCV NS5A interacts with HSC70, a key component of the CMA machinery, and recruits HSC70 to HNF-1α to target HNF-1α for CMA-mediated lysosomal degradation, thereby facilitating HCV pathogenesis. We discovered a role of HCV NS5A in CMA-dependent degradation of HNF-1α. Our results may lead to a better understanding of the role of CMA in the pathogenesis of HCV.

MODY due to hepatocyte nuclear factor 1-beta mutations (revision number 11)

2014 ◽  
Author(s):  
K Owen ◽  
G Thanabalasingham ◽  
F Kavvoura ◽  
AJ Juszczak
Keyword(s):  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Nuclear Factor 1
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