MCP-1-induced protein-1,an immune regulator

MCP-1-induced protein-1(MCPIP1)is a newly identified protein that is crucial to immune regulation.Mice lack-ing MCPIP1 gene suffer from severe immune disorders,and most of them cannot survive longer than 12 weeks.Considerable progress has been made in revealing the mechanism underlying the immune regulatory function of MCPIP1.MCPIP1 can act as an RNase to promote the mRNA degradation of some inflammatory cytokines,such as IL-6 and IL-1.Pre-microRNAs are also confirmed to be the substrate of MCPIP1 RNase.The structure of MCPIP1 N-terminal conserved domain shows a PilT N-terminus-like RNase structure,further supporting the notion that MCPIP1 has RNase activity.MCPIP1 can also deubiquitinate TNF receptor-associated factor family proteins,which are known to mediate immune and inflammatory responses.In this review,we summarize recent progress on the immune regulatory role of MCPIP1 and discuss the mechanisms underlying its function.

Structural study of the Cdc25 domain from Ral-specific guanine-nucleotide exchange factor RalGPS1a

The guanine-nucleotide exchange factor(GEF)RalGPS1a activates small GTPase Ral proteins such as RalA and RalB by stimulating the exchange of Ral bound GDP to GTP,thus regulating various downstream cellular processes.RalGPS1a is composed of an Nterminal Cdc25-like catalytic domain,followed by a PXXP motif and a C-terminal pleckstrin homology(PH)domain.The Cdc25 domain of RalGPS1a,which shares about 30%sequence identity with other Cdc25-domain proteins,is thought to be directly engaged in binding and activating the substrate Ral protein.Here we report the crystal structure of the Cdc25 domain of RalGPS1a.The bowl shaped structure is homologous to the Cdc25 domains of SOS and RasGRF1.The most remarkable difference between these three Cdc25 domains lies in their active sites,referred to as the helical hairpin region.Consistent with previous enzymological studies,the helical hairpin of RalGPS1a adopts a conformation favorable for substrate binding.A modeled RalGPS1a-RalA complex structure reveals an extensive binding surface similar to that of the SOS-Ras complex.However,analysis of the electrostatic surface potential suggests an interaction mode between the RalGPS1a active site helical hairpin and the switch 1 region of substrate RalA distinct from that of the SOS-Ras complex.