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MOLECULAR BIOLOGY: HNFs--Linking the Liver and Pancreatic Islets in Diabetes
Rohit N. Kulkarni and C. Ronald Kahn
Understanding the transcriptional regulatory networks that operate in different tissues may provide some mechanistic insight into certain diseases. In their Perspective, Kulkarni and Kahn discuss new work (Odom et al.) that identifies transcriptional regulatory networks in human liver cells and islet cells, and highlights a defect in one transcription factor in this circuitry that may contribute to late-onset type 2 diabetes.
The authors are in the Department of Cell and Molecular Physiology, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA 02215, USA. E-mail: rohit.kulkarni {at}joslin.harvard.edu
The editors suggest the following Related Resources on Science sites:
In Science Magazine
REPORTS
Duncan T. Odom, Nora Zizlsperger, D. Benjamin Gordon, George W. Bell, Nicola J. Rinaldi, Heather L. Murray, Tom L. Volkert, Jörg Schreiber, P. Alexander Rolfe, David K. Gifford, Ernest Fraenkel, Graeme I. Bell, and Richard A. Young (27 February 2004) Science303 (5662), 1378.
[DOI: 10.1126/science.1089769] |Abstract »|Full Text »|PDF »|Supporting Online Material »
Proteomic Analysis of Native Hepatocyte Nuclear Factor-4{alpha} (HNF4{alpha}) Isoforms, Phosphorylation Status, and Interactive Cofactors.
K. Daigo, T. Kawamura, Y. Ohta, R. Ohashi, S. Katayose, T. Tanaka, H. Aburatani, M. Naito, T. Kodama, S. Ihara, et al. (2011)
J. Biol. Chem.
286, 674-686
|Abstract »|Full Text »|PDF »
Distinct Regulation of Hepatic Nuclear Factor 1{alpha} by NKX6.1 in Pancreatic Beta Cells.
W. Donelan, V. Koya, S. W. Li, and L. J. Yang (2010)
J. Biol. Chem.
285, 12181-12189
|Abstract »|Full Text »|PDF »
Structural Basis of Natural Promoter Recognition by a Unique Nuclear Receptor, HNF4{alpha}: DIABETES GENE PRODUCT.
P. Lu, G. B. Rha, M. Melikishvili, G. Wu, B. C. Adkins, M. G. Fried, and Y.-I. Chi (2008)
J. Biol. Chem.
283, 33685-33697
|Abstract »|Full Text »|PDF »
Proteomic screen defines the hepatocyte nuclear factor 1{alpha}-binding partners and identifies HMGB1 as a new cofactor of HNF1{alpha}.
M. Yu, J. Wang, W. Li, Y. Z. Yuan, C. Y. Li, X. H. Qian, W. X. Xu, Y. Q. Zhan, and X. M. Yang (2008)
Nucleic Acids Res.
36, 1209-1219
|Abstract »|Full Text »|PDF »
Insulin protects islets from apoptosis via Pdx1 and specific changes in the human islet proteome.
J. D. Johnson, E. Bernal-Mizrachi, E. U. Alejandro, Z. Han, T. B. Kalynyak, H. Li, J. L. Beith, J. Gross, G. L. Warnock, R. R. Townsend, et al. (2006)
PNAS
103, 19575-19580
|Abstract »|Full Text »|PDF »
Common Variants in Maturity-Onset Diabetes of the Young Genes Contribute to Risk of Type 2 Diabetes in Finns.
L. L. Bonnycastle, C. J. Willer, K. N. Conneely, A. U. Jackson, C. P. Burrill, R. M. Watanabe, P. S. Chines, N. Narisu, L. J. Scott, S. T. Enloe, et al. (2006)
Diabetes
55, 2534-2540
|Abstract »|Full Text »|PDF »
Alterations in growth and apoptosis of insulin receptor substrate-1-deficient {beta}-cells.
A. M. Hennige, U. Ozcan, T. Okada, U. S. Jhala, M. Schubert, M. F. White, and R. N. Kulkarni (2005)
Am J Physiol Endocrinol Metab
289, E337-E346
|Abstract »|Full Text »|PDF »
HNF1{beta}/TCF2 mutations impair transactivation potential through altered co-regulator recruitment.
E. Barbacci, A. Chalkiadaki, C. Masdeu, C. Haumaitre, L. Lokmane, C. Loirat, S. Cloarec, I. Talianidis, C. Bellanne-Chantelot, and S. Cereghini (2004)
Hum. Mol. Genet.
13, 3139-3149
|Abstract »|Full Text »|PDF »
cells, and highlights a defect in one transcription factor in this circuitry that may contribute to late-onset type 2 diabetes.
