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J Biol Chem, Vol. 275, Issue 12, 8540-8548, March 24, 2000
From INSERM U 135 Hormones, Genes et Reproduction, Hôpital de
Bicêtre, 78 rue du Général Leclerc,
94275 Le Kremlin Bicêtre, France
JAB1 (Jun activation
domain-binding protein-1) has previously been
described as a coactivator of AP1 transcription factor. We show here,
by yeast and mammalian two-hybrid analyses and by pull-down
experiments, that JAB1 also interacts with both the progesterone
receptor (PR) and the steroid receptor coactivator 1 (SRC-1) and that
it stabilizes PR-SRC-1 complexes. We also show that JAB1 potentiates
the activity of a variety of transcription factors known to associate
with SRC-1 (nuclear receptors, activator protein-1, and nuclear factor
JAB1 Interacts with Both the Progesterone Receptor and SRC-1*
,
B). This occurs without any modification of PR or SRC-1
concentration. JAB1 is a subunit of a large multiprotein complex that
has been called the COP9 signalosome. The latter is present in plant
and animal cells and has been shown to be involved in a variety of
cellular mechanisms including transcription regulation, cell cycle
control, and phosphorylation cascades. We now show that it is also
involved in the mechanisms of action of nuclear receptors and of their coactivators.
*
This work was supported by INSERM, the Association pour la
Recherche sur le Cancer, the Ligue contre le Cancer, the Faculté de Médecine Paris-Sud, and the Fondation pour la Recherche
Médicale.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.
Recipient of a fellowship from the A. Onasis Foundation of Greece.
§
Recipient of a grant from the Association pour la Recherche sur le Cancer.
¶
To whom correspondence should be addressed. Tel.:
33-1-45-21-33-29; Fax: 33-1-45-21-27-51; E-mail:
u135@kb.inserm.fr.
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