Cloning and characterization of murine glial cell-derived neurotrophic factor inducible transcription factor (MGIF).
The potent neurotrophic factor glial cell-derived neurotrophic factor (GDNF) is a distant member of the transforming growth factor-beta (TGF-beta) superfamily of proteins. We report a transcription factor that is the first nuclear protein known to be induced by GDNF, thus designated murine GDNF inducible factor (mGIF). The cDNA was cloned in the course of investigating transcription factors that bind to Sp1 consensus sequences, using the in situ filter detection method, and it was found to encode a protein having the same C2-H2 zinc finger motif as Sp1. Sequence analysis indicated that mGIF is homologous to the human TGF-beta inducible early gene (TIEG) and human early growth response gene-alpha (EGR-alpha). mGIF is widely distributed in the adult mouse with high mRNA levels in kidney, lung, brain, liver, heart, and testis. In the adult brain, mGIF is abundantly expressed in hippocampus, cerebral cortex, cerebellum, and amygdala with lower amounts in striatum, nucleus accumbens, olfactory tubercle, thalamus, and substantia nigra. During development, mGIF mRNA also has a wide distribution, including in cerebral cortex, cerebellar primordium, kidney, intestine, liver, and lung. GDNF induces the expression of mGIF rapidly and transiently both in a neuroblastoma cell line and in primary cultures of rat embryonic cortical neurons. Co-transfection of the Drosophila SL2 cells using mGIF expression plasmid and reporter constructs having Sp1 binding sites indicated that mGIF represses transcription from a TATA-containing as well as from a TATA-less promoter. These observations suggest that the zinc finger transcription factor mGIF could be important in mediating some of the biological effects of GDNF.
Yajima
S
S
Genetic Pharmacology Unit, Experimental Therapeutics Branch, National Institute of Neurological Diseases and Stroke, Bethesda, Maryland 20892, USA.
Lammers
C H
CH
Lee
S H
SH
Hara
Y
Y
Mizuno
K
K
Mouradian
M M
MM
D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D001923:Brain Chemistry / Q000502:physiology; D002460:Cell Line; D003001:Cloning, Molecular; D004247:DNA / Q000032:analysis; D015342:DNA Probes; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051379:Mice; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009447:Neuroblastoma; D018696:Neuroprotective Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D012097:Repressor Proteins; D016329:Sp1 Transcription Factor / Q000737:chemistry / Q000235:genetics; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016335:Zinc Fingers / Q000502:physiology; D051741:Kruppel-Like Transcription Factors; D051765:Early Growth Response Transcription Factors
D004247:DNA; D015342:DNA Probes; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D012097:Repressor Proteins; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; C495040:Gdnf protein, mouse; C495041:Gdnf protein, rat; C491385:Klf10 protein, rat; C569958:KLF10 protein, mouse; D051741:Kruppel-Like Transcription Factors; D051765:Early Growth Response Transcription Factors