AN INHIBITOR DOMAIN IN C-FOS REGULATES ACTIVATION DOMAINS CONTAINING THE HOB1 MOTIF

The c-Fos protein has three activation modules at its C-terminus, two of which contain moths (HOB1 and HOB2) which are also present in the a ctivation domains of c-Jun. Here we show the existence of two addition al activation modules at the N-terminus of c-Fos, one of which contain s a second HOB1 motif (HOB1-N). The N-terminus also contains an inhibi tor domain (ID1) which silences HOB1 activity. GAL4 fusion experiments showed that ID1 can specifically silence HOB1-containing activation d omains from c-Fos or c-Jun when linked in cis, but will not affect oth er 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 r equired for inhibitor function. Mutagenesis of IM1 enhances the abilit y of c-Fos to activate an AP1 bearing promoter. Finally, squelching ex periments 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 se quence specific manner to inhibit a subset of activation domains.