Abstract 5279: MCPIP1 is an Inducible Corepressor of NF-KappaB
The transcription factor NF-κB is a central regulator of host immune and inflammatory response. However, excessive and prolonged activation of NF-κB can cause massive damage to host tissues and can result in human inflammatory diseases, such as atherosclerosis and arthritis. Thus, NF-κB activation must be terminated at the appropriate time points. MCPIP1 is a recent identified CCCH-type zinc finger containing protein, which is significantly induced by MCP-1 treatment of human monocytes and thus designated as MCP-induced protein1 (MCPIP1). Here we report that MCPIP1 function as an inducible corepressor of NF-κB to feedback control NF-κB activation. In the transfection experiments, MCPIP1 dose-dependently inhibits inflammatory stimuli-induced NF-κB reporter activity. Overexpression of MCPIP1 does not affect TNFα-initiated IKK activation, NF-κB translocation and DNA binding. Further study reveals that MCPIP1 can directly bind to p65 of NF-κB and recruit NCoR and HDAC1 to form repressing complex, which blocks NF-κB target gene expression. Interestingly, the same stimuli that induce NF-κB activation also can induce MCPIP1 expression and translocation into nucleus. Taken together, our results suggest that MCPIP1 is a novel inducible corepressor of NF-κB and may be a critical player in host immune and inflammatory response.
This research has received full or partial funding support from the American Heart Association, AHA Greater Southeast Affiliate (Alabama, Florida, Georgia, Louisiana, Mississippi, Puerto Rico & Tennessee).