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J Biol Chem, Vol. 275, Issue 7, 4774-4782, February 18, 2000
From the Zentrum für Molekulare Neurobiologie,
Universität Hamburg, Martinistrasse 52, D-20246 Hamburg, Germany
The glial cells missing (GCM) family of
transcription factors consists of Drosophila GCM and the
mammalian proteins GCMa and GCMb. They are expressed in a highly
restricted manner during development and are known or assumed to be
important regulators of developmental fate decisions. As the
biochemical properties of GCMb have not been studied so far, we have
undertaken a detailed structure-function analysis of the mouse GCMb
(mGCMb) protein. DNA-binding specificity was very similar to that of
other GCM proteins. Nevertheless, mGCMb was only a weak transcriptional activator in a number of different tissue culture systems.
Interestingly, this was not due to an intrinsic absence of
transactivation potential. In effect, we were able to identify two
separate transactivation domains within mGCMb, one carboxyl-terminally
adjacent to the DNA-binding domain and the second within the extreme
carboxyl terminus. Activity of both transactivation domains was,
however, modulated by an inhibitory region unique to mGCMb and located between the two transactivation domains. Furthermore, pulse-chase experiments proved that the mGCMb protein has a half-life approximately four times shorter than mGCMa. Introduction of the above mentioned inhibitory domain of mGCMb into mGCMa shortened the half-life of mGCMa
to a value typical of mGCMb with a concomitant reduction in
transactivation potential. Given the strong correlation between protein
stability and transactivation potential, functional differences between
the two mammalian GCM homologs are likely due to differences in
stability with a single inhibitory region in mGCMb being involved in
the reduction of both.
Protein Stability and Domain Topology Determine the
Transcriptional Activity of the Mammalian Glial Cells Missing
Homolog, GCMb*
,, and
*
This work was supported by Grant SFB 444 from the Deutsche
Forschungsgemeinschaft (to M. W.).The costs of publication of this article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Contributed equally to this work.
§
To whom correspondence should be addressed. Tel.: 49 40 42803 6274;
Fax: 49 40 42803 6602; E-mail:
wegner@plexus.uke.uni-hamburg.de.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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