Advertisement
JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a Letter to Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Vaxillaire, M.
Right arrow Articles by Pontoglio, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vaxillaire, M.
Right arrow Articles by Pontoglio, M.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

J Biol Chem, Vol. 274, Issue 50, 35639-35646, December 10, 1999

Anatomy of a Homeoprotein Revealed by the Analysis of Human MODY3 Mutations*

Martine VaxillaireDagger §, Amar Abderrahmani§, Philippe Boutin§, Bernard Bailleul§, Philippe Froguel§, Moshe YanivDagger ||, and Marco PontoglioDagger

From the Dagger  Unité des Virus Oncogènes, Unité de Recherche Associée 1644, Centre National de la Recherche Scientifique, Département des Biotechnologies, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France and § Institut de Biologie de Lille, Unité Propre de Recherche et d'Enseignement Supérieur A 8090, Centre National de la Recherche Scientifique, Institut Pasteur de Lille, 1 rue du Professeur Calmette, BP 245, 59019 Lille, France

Hepatocyte nuclear factor 1alpha (HNF1alpha ) is an atypical dimeric homeodomain-containing protein that is expressed in liver, intestine, stomach, kidney, and pancreas. Mutations in the HNF1alpha gene are associated with an autosomal dominant form of non-insulin-dependent diabetes mellitus called maturity-onset diabetes of the young (MODY3). More than 80 different mutations have been identified so far, many of which involve highly conserved amino acid residues among vertebrate HNF1alpha . In the present work, we investigated the molecular mechanisms by which MODY3 mutations could affect HNF1alpha function. For this purpose, we analyzed the properties of 10 mutants resulting in amino acid substitutions or protein truncation. Some mutants have a reduced protein stability, whereas others are either defective in the DNA binding or impaired in their intrinsic trans-activation potential. Three mutants, characterized by a complete loss of trans-activation, behave as dominant negatives when transfected with the wild-type protein. These data define a clear causative relationship between MODY3 mutations and functional defects in HNF1alpha trans-activation. In addition, our analysis sheds new light on the structure of a homeoprotein playing a key role in pancreatic beta  cell function.

* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Present address: Institut de Biologie de Lille, Unité Propre de Recherche et d'Enseignement Supérieur A 8090, Centre National de la Recherche Scientifique, Institut Pasteur de Lille, 1 rue du Professeur Calmette, BP 245, 59019 Lille, France.

|| To whom correspondence should be addressed: Unité des Virus Oncogènes, Unité de Recherche Associée 1644, Centre National de la Recherche Scientifique, Département des Biotechnologies, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France. Tel.: 33-1-45-68-85-12; Fax: 33-1-40-61-30-33; E-mail: yaniv@pasteur.fr.

Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 DiabetesHome page
L. W. Harries, M. J. Sloman, E. A.C. Sellers, A. T. Hattersley, and S. Ellard
Diabetes Susceptibility in the Canadian Oji-Cree Population Is Moderated by Abnormal mRNA Processing of HNF1A G319S Transcripts
Diabetes, July 1, 2008; 57(7): 1978 - 1982.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
M. Vaxillaire and P. Froguel
Monogenic Diabetes in the Young, Pharmacogenetics and Relevance to Multifactorial Forms of Type 2 Diabetes
Endocr. Rev., May 1, 2008; 29(3): 254 - 264.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
C. Bellanne-Chantelot, C. Carette, J.-P. Riveline, R. Valero, J.-F. Gautier, E. Larger, Y. Reznik, P.-H. Ducluzeau, A. Sola, A. Hartemann-Heurtier, et al.
The Type and the Position of HNF1A Mutation Modulate Age at Diagnosis of Diabetes in Patients with Maturity-Onset Diabetes of the Young (MODY)-3
Diabetes, February 1, 2008; 57(2): 503 - 508.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. D. Tward, K. D. Jones, S. Yant, S. T. Cheung, S. T. Fan, X. Chen, M. A. Kay, R. Wang, and J. M. Bishop
Distinct pathways of genomic progression to benign and malignant tumors of the liver
PNAS, September 11, 2007; 104(37): 14771 - 14776.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
W. Winckler, M. N. Weedon, R. R. Graham, S. A. McCarroll, S. Purcell, P. Almgren, T. Tuomi, D. Gaudet, K. B. Bostrom, M. Walker, et al.
Evaluation of Common Variants in the Six Known Maturity-Onset Diabetes of the Young (MODY) Genes for Association With Type 2 Diabetes
Diabetes, March 1, 2007; 56(3): 685 - 693.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
L. W. Harries, S. Ellard, A. Stride, The European MODY consortium, N. G. Morgan, and A. T. Hattersley
Isomers of the TCF1 gene encoding hepatocyte nuclear factor-1 alpha show differential expression in the pancreas and define the relationship between mutation position and clinical phenotype in monogenic diabetes
Hum. Mol. Genet., July 15, 2006; 15(14): 2216 - 2224.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
C. W. Rowley, L. J. Staloch, J. K. Divine, S. P. McCaul, and T. C. Simon
Mechanisms of mutual functional interactions between HNF-4{alpha} and HNF-1{alpha} revealed by mutations that cause maturity onset diabetes of the young
Am J Physiol Gastrointest Liver Physiol, March 1, 2006; 290(3): G466 - G475.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
E. Barbacci, A. Chalkiadaki, C. Masdeu, C. Haumaitre, L. Lokmane, C. Loirat, S. Cloarec, I. Talianidis, C. Bellanne-Chantelot, and S. Cereghini
HNF1{beta}/TCF2 mutations impair transactivation potential through altered co-regulator recruitment
Hum. Mol. Genet., December 15, 2004; 13(24): 3139 - 3149.
[Abstract] [Full Text] [PDF]

Home page
 ANN INTERN MEDHome page
C. Bellanne-Chantelot, D. Chauveau, J.-F. Gautier, D. Dubois-Laforgue, S. Clauin, S. Beaufils, J.-M. Wilhelm, C. Boitard, L.-H. Noel, G. Velho, et al.
Clinical Spectrum Associated with Hepatocyte Nuclear Factor-1{beta} Mutations
Ann Intern Med, April 6, 2004; 140(7): 510 - 517.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
L. W. Harries, A. T. Hattersley, and S. Ellard
Messenger RNA Transcripts of the Hepatocyte Nuclear Factor-1{alpha} Gene Containing Premature Termination Codons Are Subject to Nonsense-Mediated Decay
Diabetes, February 1, 2004; 53(2): 500 - 504.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
S. B. Smith, R. Gasa, H. Watada, J. Wang, S. C. Griffen, and M. S. German
Neurogenin3 and Hepatic Nuclear Factor 1 Cooperate in Activating Pancreatic Expression of Pax4
J. Biol. Chem., October 3, 2003; 278(40): 38254 - 38259.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
J. K. Divine, S. P. McCaul, and T. C. Simon
HNF-1{alpha} and endodermal transcription factors cooperatively activate Fabpl: MODY3 mutations abrogate cooperativity
Am J Physiol Gastrointest Liver Physiol, June 9, 2003; 285(1): G62 - G72.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
L. Bjorkhaug, J. V. Sagen, P. Thorsby, O. Sovik, A. Molven, and P. R. Njolstad
Hepatocyte Nuclear Factor-1{alpha} Gene Mutations and Diabetes in Norway
J. Clin. Endocrinol. Metab., February 1, 2003; 88(2): 920 - 931.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes CareHome page
A. Stride, M. Shepherd, T. M. Frayling, M. P. Bulman, S. Ellard, and A. T. Hattersley
Intrauterine Hyperglycemia Is Associated With an Earlier Diagnosis of Diabetes in HNF-1{alpha} Gene Mutation Carriers
Diabetes Care, December 1, 2002; 25(12): 2287 - 2291.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes CareHome page
T. Klupa, J. H. Warram, A. Antonellis, M. Pezzolesi, M. Nam, M. T. Malecki, A. Doria, S. S. Rich, and A. S. Krolewski
Determinants of the Development of Diabetes (Maturity-Onset Diabetes of the Young-3) in Carriers of HNF-1{alpha} Mutations: Evidence for parent-of-origin effect
Diabetes Care, December 1, 2002; 25(12): 2292 - 2301.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
J. Ferrer
A Genetic Switch in Pancreatic {beta}-Cells: Implications for Differentiation and Haploinsufficiency
Diabetes, August 1, 2002; 51(8): 2355 - 2362.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
B. L. Triggs-Raine, R. D. Kirkpatrick, S. L. Kelly, L. D. Norquay, P. A. Cattini, K. Yamagata, A. J. G. Hanley, B. Zinman, S. B. Harris, P. H. Barrett, et al.
HNF-1alpha G319S, a transactivation-deficient mutant, is associated with altered dynamics of diabetes onset in an Oji-Cree community
PNAS, April 2, 2002; 99(7): 4614 - 4619.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
J. Eeckhoute, P. Formstecher, and B. Laine
Maturity-Onset Diabetes of the Young Type 1 (MODY1)-Associated Mutations R154X and E276Q in Hepatocyte Nuclear Factor 4{{alpha}} (HNF4{{alpha}}) Gene Impair Recruitment of p300, a Key Transcriptional Coactivator
Mol. Endocrinol., July 1, 2001; 15(7): 1200 - 1210.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
M. PONTOGLIO
Hepatocyte Nuclear Factor 1, a Transcription Factor at the Crossroads of Glucose Homeostasis
J. Am. Soc. Nephrol., November 1, 2000; 11(90002): S140 - S143.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
B. L. Triggs-Raine, R. D. Kirkpatrick, S. L. Kelly, L. D. Norquay, P. A. Cattini, K. Yamagata, A. J. G. Hanley, B. Zinman, S. B. Harris, P. H. Barrett, et al.
HNF-1alpha G319S, a transactivation-deficient mutant, is associated with altered dynamics of diabetes onset in an Oji-Cree community
PNAS, April 2, 2002; 99(7): 4614 - 4619.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 1999 by the American Society for Biochemistry and Molecular Biology.
Advertisement
spacer
Advertisement
Advertisement