The MafA transcription factor appears to be responsible for tissue-specific expression of insulin

被引:223
作者
Matsuoka, T
Artner, I
Henderson, E
Means, A
Sander, M
Stein, R
机构
[1] Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA
[2] Vanderbilt Univ, Sch Med, Dept Surg Oncol, Nashville, TN 37232 USA
[3] Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92697 USA
关键词
D O I
10.1073/pnas.0306233101
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Insulin gene expression is regulated by several islet-enriched transcription factors. However, MafA is the only beta cell-specific activator. Here, we show that MafA selectively induces endogenous insulin transcription in non-beta cells. MafA was also first detected in the insulin-producing cells formed during the second and predominant phase of 6 cell differentiation, and absent in the few insulin-positive cells found in Nkx6.1(-/-) pancreata, which lack the majority of second-phase beta cells. These results demonstrate that MafA is a potent insulin activator that is likely to function downstream of Nkx6.1 during islet insulin-producing cell development.
引用
收藏
页码:2930 / 2933
页数:4
相关论文
共 32 条
[21]   Interaction of Maf transcription factors with Pax-6 results in synergistic activation of the glucagon promoter [J].
Planque, N ;
Leconte, L ;
Coquelle, FM ;
Benkhelifa, S ;
Martin, P ;
Felder-Schmittbuhl, MP ;
Saule, S .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (38) :35751-35760
[22]   The islet β cell-enriched RIPE3b1/Maf transcription factor regulates pdx-1 expression [J].
Samaras, SE ;
Zhao, L ;
Means, A ;
Henderson, E ;
Matsuoka, T ;
Stein, R .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (14) :12263-12270
[23]   Genetic analysis reveals that PAX6 is required for normal transcription of pancreatic hormone genes and islet development [J].
Sander, M ;
Neubuser, A ;
Kalamaras, J ;
Ee, HC ;
Martin, GR ;
German, MS .
GENES & DEVELOPMENT, 1997, 11 (13) :1662-1673
[24]  
Sander M, 2000, DEVELOPMENT, V127, P5533
[25]   THE ROLE OF THE INSULIN CONTROL ELEMENT AND RIPE3B1 ACTIVATORS IN GLUCOSE-STIMULATED TRANSCRIPTION OF THE INSULIN GENE [J].
SHARMA, A ;
FUSCODEMANE, D ;
HENDERSON, E ;
EFRAT, S ;
STEIN, R .
MOLECULAR ENDOCRINOLOGY, 1995, 9 (11) :1468-1476
[26]  
SHIEH SY, 1991, J BIOL CHEM, V266, P16708
[27]  
STEIN R, 2001, HDB PHYSL 7, V2, P25
[28]   Early-onset type-II diabetes mellitus (MODY4) linked to IPF1 [J].
Stoffers, DA ;
Ferrer, J ;
Clarke, WL ;
Habener, JF .
NATURE GENETICS, 1997, 17 (02) :138-139
[29]   Pax6 Is required for differentiation of glucagon-producing alpha-cells in mouse pancreas [J].
StOnge, L ;
SosaPineda, B ;
Chowdhury, K ;
Mansouri, A ;
Gruss, P .
NATURE, 1997, 387 (6631) :406-409
[30]   Gene expression cascades in pancreatic development [J].
Wilson, ME ;
Scheel, D ;
German, MS .
MECHANISMS OF DEVELOPMENT, 2003, 120 (01) :65-80