Brown H J, Sutherland J A, Cook A, Bannister A J, Kouzarides T
Wellcome/CRC Institute, Cambridge, UK.
EMBO J. 1995 Jan 3;14(1):124-31. doi: 10.1002/j.1460-2075.1995.tb06982.x.
The c-Fos protein has three activation modules at its C-terminus, two of which contain motifs (HOB1 and HOB2) which are also present in the activation domains of c-Jun. Here we show the existence of two additional activation modules at the N-terminus of c-Fos, one of which contains a second HOB1 motif (HOB1-N). The N-terminus also contains an inhibitor domain (ID1) which silences HOB1 activity. GAL4 fusion experiments showed that ID1 can specifically silence HOB1-containing activation domains from c-Fos or c-Jun when linked in cis, but will not affect other distinct activation domains. The c-Fos related protein, FosB, also contains an inhibitor domain. Mutagenic and deletion analyses identify an inhibitor motif (IM1) conserved between c-Fos and FosB, which is required for inhibitor function. Mutagenesis of IM1 enhances the ability of c-Fos to activate an AP1 bearing promoter. Finally, squelching experiments suggest that c-Fos ID1 binds a limiting protein involved in inhibition. These results demonstrate the existence of a new class of inhibitor domain within transcriptional activators, which acts in a sequence specific manner to inhibit a subset of activation domains.
c-Fos蛋白在其C末端有三个激活模块，其中两个包含与c-Jun激活域中相同的基序（HOB1和HOB2）。在此我们展示了c-Fos在N末端还存在另外两个激活模块，其中一个包含第二个HOB1基序（HOB1-N）。N末端还包含一个抑制域（ID1），可使HOB1活性沉默。GAL4融合实验表明，当顺式连接时，ID1可特异性沉默c-Fos或c-Jun中含HOB1的激活域，但不会影响其他不同的激活域。与c-Fos相关的蛋白FosB也含有一个抑制域。诱变和缺失分析确定了c-Fos和FosB之间保守的一个抑制基序（IM1），这是抑制功能所必需的。IM1诱变增强了c-Fos激活含AP1启动子的能力。最后，压制实验表明c-Fos ID1结合一种参与抑制作用的受限蛋白。这些结果证明转录激活因子中存在一类新的抑制域，其以序列特异性方式作用，抑制一部分激活域。
