Functional screening of five PYPAF family members identifies PYPAF5 as a novel regulator of NF‐κB and caspase‐1

FEBS Letters

DiStefano, Peter S.¹  Briskin, Michael¹  Huang, Waan-Jeng¹  Grenier, Jill M.¹  Kelly, Roxanne¹  Al-Garawi, Amal¹  Wang, Lin¹  Bertin, John¹  Lora, Jose M.¹  Merriam, Sarah¹  Carlson, Adam¹  Manji, Gulam A.¹ 

[1] Millennium Pharmaceuticals Inc., 75 Sidney Street, Cambridge, MA 02139, USA

关键词: PYPAF5;    PYRIN-containing Apaf-1-like protein;    Caspase-1;    NF-κB;    ASC;    Inflammation;   

DOI  :  10.1016/S0014-5793(02)03416-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

PYRIN-containing Apaf-1-like proteins (PYPAFs) are a recently identified family of proteins thought to function in apoptotic and inflammatory signaling pathways. PYPAF1 and PYPAF7 proteins have been found to assemble with the PYRIN–CARD protein ASC and coordinate the activation of NF-κB and pro-caspase-1. To determine if other PYPAF family members function in pro-inflammatory signaling pathways, we screened five other PYPAF proteins (PYPAF2, PYPAF3, PYPAF4, PYPAF5 and PYPAF6) for their ability to activate NF-κB and pro-caspase-1. Co-expression of PYPAF5 with ASC results in a synergistic activation of NF-κB and the recruitment of PYPAF5 to punctate structures in the cytoplasm. The expression of PYPAF5 is highly restricted to granulocytes and T-cells, indicating a role for this protein in inflammatory signaling. In contrast, PYPAF2, PYPAF3, PYPAF4 and PYPAF6 failed to colocalize with ASC and activate NF-κB. PYPAF5 also synergistically activated caspase-1-dependent cytokine processing when co-expressed with ASC. These findings suggest that PYPAF5 functions in immune cells to coordinate the transduction of pro-inflammatory signals to the activation of NF-κB and pro-caspase-1.

【 授权许可】

Unknown