Characterization of metal-responsive transcription factor (MTF-1) from the giant rodent capybara reveals features in common with human as well as with small rodents (mouse, rat). Short communication.
From mammals to insects, metal-responsive transcription factor 1 (MTF-1) is essential for the activation of metallothionein genes upon heavy-metal load. We have previously found that human MTF-1 induces a stronger metal response than mouse MTF-1. The latter differs from the human one in a number of amino acid positions and is also shorter by 78 aa at its C-terminus. We reasoned that the weaker metal inducibility might be associated with a lesser demand for tight metal homeostasis in a low-weight, short-lived animal, and thus set out to determine the sequence of MTF-1 from the largest living rodent, the Brazilian capybara that can reach 65 kg and also has a considerably longer life span than smaller rodents. An expression clone for capybara MTF-1 was then tested for its activity in both mouse and human cells. Our analysis revealed three unexpected features: i) capybara MTF-1 in terms of amino acid sequence is much more closely related to human than to mouse MTF-1, suggesting an accelerated evolution of MTF-1 in the evolutionary branch leading to small rodents; ii) capybara MTF-1 is even 32 aa shorter at its C-terminus than mouse MTF-1, and iii) in an activity test, it is not more active than mouse MTF-1. The latter two findings might indicate that capybara has evolved in an environment with low heavy-metal load.
Lindert
Uschi
U
Institute of Molecular Biology, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, (fax: +41-44-635 6811).
Leuzinger
Lucas
L
Institute of Molecular Biology, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, (fax: +41-44-635 6811).
Steiner
Kurt
K
Institute of Molecular Biology, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, (fax: +41-44-635 6811).
Georgiev
Oleg
O
Institute of Molecular Biology, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, (fax: +41-44-635 6811).
Schaffner
Walter
W
Institute of Molecular Biology, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, (fax: +41-44-635 6811).
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D008668:Metallothionein / Q000737:chemistry / Q000235:genetics; D019216:Metals, Heavy / Q000737:chemistry; D051379:Mice; D008969:Molecular Sequence Data; D051381:Rats; D012377:Rodentia; D016415:Sequence Alignment; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D014162:Transfection; D000097809:Transcription Factor MTF-1
D004247:DNA; D004268:DNA-Binding Proteins; D008668:Metallothionein; D019216:Metals, Heavy; D014157:Transcription Factors; D000097809:Transcription Factor MTF-1