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Locus That Encode Inhibitors of Retinoic Acid Receptor- and Triiodothyronine Receptor Activities
Laboratoire de Biologie Moléculaire et Cellulaire (A.F.,
O.C., K.G., F.F., C.L., P.S., J.S.) Centre Nationale de la
Recherche Scientifique UMR 49, Institut Nationale de la Recherche
Agronomique LA 913 Ecole Normale Supérieure de Lyon 69364
Lyon Cedex 07, France
1 Unité d’Oncologie
Moléculaire (V.L.) Institut Pasteur 59019 Lille,
France
The thyroid hormone receptor-coding locus,
c-erbA
, generates several mRNAs originating from a single primary
transcript that undergoes alternative splicing. We have identified for
the first time two new transcripts, called TR
1 and TR2
[mRNA for isoform 1 and 2 of the T3
receptor (TR), respectively], whose transcription is initiated from an
internal promoter located within intron 7 of the c-erbA gene. These
two new transcripts exhibit tissue-specific patterns of expression in
the mouse. These two patterns are in sharp contrast with the expression
patterns of the full-length transcripts generated from the c-erbA
locus. TR1 and TR2 mRNAs encode N-terminally truncated
isoforms of T3R1 and T3R2, respectively. The protein product of
TR1 antagonizes the transcriptional activation elicited by
T3 and retinoic acid. This protein inhibits the
ligand-induced activating functions of T3R1 and
9-cis-retinoic acid receptor- but does not affect the
retinoic acid-dependent activating function of retinoic acid
receptor-. We predict that these truncated proteins may work as
down-regulators of transcriptional activity of nuclear hormone
receptors in vivo.
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