毒素T3DB ID

T3D3774

目标BioDB ID

BE0004924

目标名称

activator protein 1

目标UniProt ID

P18846; P15336; P18847; P18848; Q9Y2D1; P18850; P17544; Q8WYK2; P01100; P05412

作用机理

Secalonic acid D (SAD) is though to induce cleft palate by causing the formation of smaller palatal shelves that fail to elevate and fuse. This inhibited palatal shelf growth is a result of the of SAD causing reduced proliferation of embryonic palatal mesenchymal (HEPM) cells. SAD binds to and phosphorylates cAMP response element binding protein (CREB), an important transcription factor required for the expression of numerous genes including proliferating cell nuclear antigen (PCNA) gene. The phosphorylation of CREB by SAD prevents it from forming the necessary transcription factor-cAMP response element complex at transcription start sites, so these genes are not expressed. This leads to reduced palatal mesenchymal cell number causing reduced palatal shelf growth and thus cleft palate. (A3088, A3089, A3090)

参考文献

A3088 - Dhulipala VC, Maddali KK, Welshons WV, Reddy CS: Secalonic acid D blocks embryonic palatal mesenchymal cell-cycle by altering the activity of CDK2 and the expression of p21 and cyclin E. Birth Defects Res B Dev Reprod Toxicol. 2005 Jun;74(3):233-42. (15880679) A3089 - Hanumegowda UM, Dhulipala VC, Reddy CS: Mechanism of secalonic acid D-induced inhibition of transcription factor binding to cyclic AMP response element in the developing murine palate. Toxicol Sci. 2002 Nov;70(1):55-62. (12388835) A3090 - Hanumegowda UM, Judy BM, Welshons WV, Reddy CS: Selective inhibition of murine palatal mesenchymal cell proliferation in vitro by secalonic acid D. Toxicol Sci. 2002 Mar;66(1):159-65. (11861983)

创建于

2010-05-26 18:10:25 UTC

更新于

2014-09-04 16:24:35 UTC