Hong Seok Jong, Chae Han, Lardaro Thomas, Hong Sunghoi, Kim Kwang-Soo
Molecular Neurobiology Laboratory, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA.
Biochem Biophys Res Commun. 2008 Apr 11;368(3):650-5. doi: 10.1016/j.bbrc.2008.01.165. Epub 2008 Feb 12.
The homeodomain transcription factor Phox2b is one of the key determinants involved in the development of noradrenergic (NA) neurons in both the central nervous system (CNS) and the peripheral nervous system (PNS). Using yeast two-hybrid screening, we isolated a Phox2b interacting protein, Trim11, which belongs to TRIM (Tripartite motif) or RBCC proteins family, and contains a RING domain, B-boxes, a coiled-coil domain, and the B30.2/SPRY domain. Protein-protein interaction assays showed that Phox2b was able to physically interact with Trim11. The B30.2/SPRY domain of Trim11 was required for the interaction with Phox2b. Expression of Phox2b and Trim11 was detected in the sympathetic ganglia (SG) of mouse embryos. Forced expression of Trim11 with Phox2b further increased mRNA levels of dopamine beta-hydroxylase (DBH) gene in primary avian neural crest stem cell (NCSC) culture. This study suggests a potential role for Trim11 in the specification of NA phenotype by interaction with Phox2b.
同源结构域转录因子Phox2b是参与中枢神经系统（CNS）和外周神经系统（PNS）中去甲肾上腺素能（NA）神经元发育的关键决定因素之一。通过酵母双杂交筛选，我们分离出一种与Phox2b相互作用的蛋白Trim11，它属于TRIM（三方基序）或RBCC蛋白家族，包含一个RING结构域、B-box结构域、一个卷曲螺旋结构域和B30.2/SPRY结构域。蛋白质-蛋白质相互作用分析表明，Phox2b能够与Trim11发生物理相互作用。Trim11的B30.2/SPRY结构域是与Phox2b相互作用所必需的。在小鼠胚胎的交感神经节（SG）中检测到了Phox2b和Trim11的表达。在原代鸟类神经嵴干细胞（NCSC）培养中，与Phox2b一起强制表达Trim11可进一步提高多巴胺β-羟化酶（DBH）基因的mRNA水平。这项研究表明Trim11通过与Phox2b相互作用在NA表型的特化中具有潜在作用。
