Naofen, a novel WD40-repeat protein, mediates spontaneous and tumor necrosis factor-induced apoptosis.
Naofen has recently been identified from the rat brain/spinal cord cDNA library as a substance reactive against an anti-shigatoxin (Stx)-2 antibody. Naofen mRNA is composed of 4620 nucleotides and encodes 1170 amino acids. Naofen contains four WD-repeat domains in its N-terminus and is ubiquitously distributed in many tissues of the rat. Tumor necrosis factor (TNF)-alpha enhanced the expression of naofen mRNA in HEK293 cells in a dose-dependent manner. Furthermore, naofen siRNA, which predominantly knocked down the expression of naofen mRNA, significantly reduced both TNF-alpha-induced caspase-3 activation and apoptosis in HEK293 cells. Overexpression of naofen in HEK293 cells (FLAG-NF) spontaneously induced caspase -3 activation and apoptosis, and showed extremely high susceptibility to TNF-alpha-induced apoptosis. These results indicated that naofen may function as a novel modulator activating caspase-3, and promoting TNF-alpha-stimulated apoptosis.
Feng
Guo-Gang
GG
Department of Pharmacology, Aichi Medical University School of Medicine, Nagakute, Aichi-gun, Aichi Pref 480-1195, Japan. fenggg@aichi-med-u.ac.jp
Li
Chang
C
Huang
Lei
L
Tsunekawa
Koji
K
Sato
Yuko
Y
Fujiwara
Yoshihiro
Y
Komatsu
Tooru
T
Honda
Takashi
T
Fan
Jun-Hua
JH
Goto
Hidemi
H
Koide
Tatsuro
T
Hasegawa
Takaaki
T
Ishikawa
Naohisa
N
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3 / Q000096:biosynthesis; D002460:Cell Line; D004789:Enzyme Activation; D006801:Humans; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; D011506:Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C582790:WDR35 protein, rat; C548806:naofen protein, human; D053148:Caspase 3