期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 284, 期 50, 页码 34531-34537出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M109.046102
关键词
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资金
- Health Research Board Science Foundation Ireland
- Wellcome Trust
Interleukin-1 beta (IL-1 beta) is an important pro-inflammatory cytokine that is secreted by unconventional means in a caspase-1-dependent manner. Using a one-step immunoprecipitation approach to isolate endogenous caspase-1 from the monocytic THP1 cell line, we identified previously undescribed binding partners using mass spectrometry. One of the proteins identified was Rab39a, a member of the Rab GTPase family, agroup of proteins that have important roles in protein trafficking and secretion. We confirmed by co-immunoprecipitation that Rab39a binds caspase-1. Knock down of Rab39a with small interfering RNA resulted in diminished levels of secreted IL-1 beta but had no effect on induction of pro-IL-1 beta mRNA by lipopolysaccharide. Rab39a contains a highly conserved caspase-1 cleavage site and was cleaved in the presence of recombinant caspase-1 or lipopolysaccharide. Finally, overexpression of Rab39a results in an increase in IL-1 beta secretion, and furthermore, overexpression of a Rab39a construct lacking the caspase-1 cleavage site leads to an additional increase in IL-1 beta secretion. Altogether, our findings show that Rab39a interacts with caspase-1 and suggest that Rab39a functions as a trafficking adaptor linking caspase-1 to IL-1 beta secretion.
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