Cloning and characterization of a small-size peptide Zfra that regulates the cytotoxic function of tumor necrosis factor by interacting with JNK1.
By cDNA library screening, here we isolated an unusual gene transcript encoding a 31-amino-acid zinc finger-like peptide that regulates apoptosis (named Zfra). Northern blotting and RT/PCR showed the transcript is abundant in spleen but absent in several prostate and breast cancer cells. When stably expressed in L929 fibroblasts, Zfra conferred resistance to the cytotoxic effects of TNF and FasL. In contrast, transiently expressed Zfra could enhance or inhibit the cytotoxicity of overexpressed death domain proteins TRADD, FADD, and RIP of the TNF signaling pathway. By GST pull-down assay and co-immunoprecipitation, TNF and UV light were shown to induce Zfra to rapidly self-associate and bind JNK1. While JNK1 is a downstream effector of the TNF signaling, Zfra regulation of the TNF cytotoxic function is likely due to its interaction, in part, with JNK1.
Hsu
Li-Jin
LJ
Guthrie Research Institute, Laboratory of Molecular Immunology, 1 Guthrie Square, Sayre, PA 18840, USA.
Schultz
Lori
L
Mattison
Jeffrey
J
Lin
Yee-Shin
YS
Chang
Nan-Shan
NS
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D002352:Carrier Proteins; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007525:Isoelectric Focusing; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*
C466684:APBB2 protein, human; D048868:Adaptor Proteins, Signal Transducing; D000906:Antibodies; C101886:Apbb2 protein, mouse; D002352:Carrier Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C505533:FADD protein, human; C505661:FASLG protein, human; C505534:Fadd protein, mouse; D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D014157:Transcription Factors; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D014409:Tumor Necrosis Factor-alpha; D048055:Mitogen-Activated Protein Kinase 8