Related Experiment Videos
Differential sensitivity of FOS and JUN family members to calpains
Abstract:
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 available for nuclear transport. Using cytoplasmic extracts from various origins, we report herein that c-FOS degradation can be initiated in a calcium-dependent manner which involves cysteine proteases called milli- and micro-calpain. Interestingly, FOS-B, a member of the fos multigene 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. FRA-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 resistant to both proteases. Given the fact that a work by others (Hiraï 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 activity through a differential control of the steady-state level of some of its components that involves calpains.
Insights
Calcium-dependent cysteine proteases, calpains, rapidly degrade c-FOS protein in the cytoplasm. This calpain activity differentially affects other Fos and Jun family members, suggesting a novel regulatory mechanism for AP-1 transcription complex activity.
Area of Science:
- Molecular Biology
- Cellular Biology
- Biochemistry
Background:
- Cytoplasmic degradation of c-FOS protein is rapid and regulates nuclear levels.
- This degradation controls the availability of full-length c-FOS for nuclear transport.
Purpose of the Study:
- To investigate the mechanism of c-FOS cytoplasmic degradation.
- To identify the proteases involved in c-FOS degradation.
- To determine the effect of these proteases on other Fos and Jun family members.
Main Methods:
- Utilized cytoplasmic extracts from various sources.
- Investigated calcium-dependent degradation pathways.
- Assessed protease sensitivity of different Fos and Jun family proteins.
Main Results:
- c-FOS degradation is initiated in a calcium-dependent manner involving milli- and micro-calpains.
- FOS-B, c-JUN, JUN-B, and JUN-D are sensitive to calpains to varying degrees.
- FRA-2 is resistant to micro-calpain but sensitive to milli-calpain, while FRA-1 is resistant to both.
Conclusions:
- Calpains play a significant role in the cytoplasmic degradation of c-FOS.
- Differential calpain sensitivity among Fos and Jun family members suggests a novel regulatory mechanism.
- This mechanism may control the steady-state levels of AP-1 transcription complex components, impacting its activity.