DIFFERENTIAL SENSITIVITY OF FOS AND JUN FAMILY MEMBERS TO CALPAINS

Degradation of c-fos protein (c-FOS) in the cytoplasm is very rapid in vivo and constitutes a crucial regulation of the nuclear steady-state level through the control of the amount of full-length molecules avai lable for nuclear transport. Using cytoplasmic extracts from various o rigins, we report herein that c-FOS degradation can be initiated in a calcium-dependent manner which involves cysteine proteases called mill i- and micro-calpain. Interestingly, FOS-B, a member of the fos multig ene family, as well as all members of the jun family (JUN-B, c-JUN and JUN-D) are also sensitive to calpains albeit to different extents. FR A-2, which is a c-FOS-related protein, is resistant to micro- but not to milli-calpain whereas FRA-1, another member of the fos family, is r esistant to both proteases. Given the fact that a work by others (Hira i et al., 1991b) suggests that calpains can be involved in c-FOS and c -JUN degradation in vivo, our observations raises the possibility of a novel contribution to the regulation of AP-1 transcription complex ac tivity through a differential control of the steady-state level of som e of its components that involves calpains.