POSH promotes cell survival in Drosophila and in human RASF cells.
In Drosophila, Eiger, a tumor necrosis factor α (TNFα) superfamily ligand, induces cell death by activating the c-Jun N-terminal kinase (JNK) pathway. Here, we report that overexpression of Plenty of SH3s (POSH) suppresses Eiger-induced cell death and produces highly deformed tissues. These results imply that high levels of POSH protect tissues from cell death. In humans, rheumatoid arthritis synovial fibroblasts (RASF) are generally resistant to apoptosis. We show that POSH is expressed at relatively high levels in RASF, and its reduction by RNAi sensitizes these cells to Fas-mediated apoptosis. Thus, we demonstrate that POSH promotes cell survival in Drosophila and in human RASF.
Department of Biological Sciences, Tokyo Metropolitan University, 1-1 Minami-osawa, Hachioji-shi, Tokyo 192-0397, Japan.
Manabu
M
Tsuda
Reimi
R
Kawaida
Kyoko
K
Kobayashi
Akira
A
Shinagawa
Tetsuji
T
Sawada
Ryo
R
Yamada
Kazuhiko
K
Yamamoto
Toshiro
T
Aigaki
D000818:Animals; D017209:Apoptosis; D001172:Arthritis, Rheumatoid / Q000473:pathology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology*; D005786:Gene Expression Regulation; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D013583:Synovial Membrane / Q000473:pathology*
C113867:CG17716 protein, Drosophila; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D008565:Membrane Proteins; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C453299:POSH protein, Drosophila; C464573:egr protein, Drosophila; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt