Characterization of the rat, mouse, and human genes of growth/differentiation factor-15/macrophage inhibiting cytokine-1 (GDF-15/MIC-1).
We have isolated the rat, mouse and human genes of a distant member of the TGF-beta superfamily, growth/differentiation factor-15/macrophage inhibiting cytokine-1 (GDF-15/MIC-1) by screening of genomic libraries. All three genes are composed of two exons, and contain one single intron that interrupts the coding sequences at identical positions within the prepro-domain of the corresponding proteins. The predicted proteins contain the structural hallmarks of members of the TGF-beta superfamily, including the seven conserved carboxy-terminal cysteine residues that form the cystine knot. The orthologous molecules show the lowest sequence conservation of all members of the TGF-beta superfamily. RT-PCR reveals an abundant expression of GDF-15/MIC-1 mRNA in numerous embryonic and adult organs and tissues. Promoter analysis of the rat promoter indicates the presence of multiple regulatory elements, including a TATA-like sequence as well as several SP1, AP-1 and AP-2 sites. Deletion analysis suggests that a 350 bp region upstream of the start of the open reading frame appears to be the most important for regulation of transcription.
Böttner
M
M
Department of Neuroanatomy, University of Heidelberg, Germany. un691mb@genius.embnet.dkfz-heidelberg.de
Laaff
M
M
Schechinger
B
B
Rappold
G
G
Unsicker
K
K
Suter-Crazzolara
C
C
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D055436:Growth Differentiation Factor 15; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid; D017386:Sequence Homology, Amino Acid; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; C526140:GDF15 protein, human; C526141:Gdf15 protein, mouse; C526142:Gdf15 protein, rat; D055436:Growth Differentiation Factor 15; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta