Oncogene 2005,
PMID: 15558021
Cuevas, Bruce D; Uhlik, Mark T; Garrington, Timothy P; Johnson, Gary L
Activator protein 1 (AP-1) transcription factor dimers are composed of Jun, Fos, and ATF member proteins, but the mechanisms that determine AP-1 composition are not clearly defined and the function of specific dimers is not well understood. MEKK1 is a mitogen-activated protein kinase (MAPK) kinase kinase and an ubiquitin ligase that regulates both the extracellular signal-regulated kinase 1/2 and the c-Jun amino-terminal kinase. Herein, we demonstrate that MEKK1 regulates the AP-1 protein repertoire. Both FGF-2 and phorbol ester-inducible urokinase-type plasminogen activator (uPA) expression requires AP-1 binding to an enhancer element in the uPA promoter, and we have previously shown that FGF-2 or PMA induction of uPA expression is strongly dependent on MEKK1. JunB mRNA is significantly increased in MEKK1-/- cells, demonstrating that MEKK1 suppresses JunB mRNA expression. Upregulation of JunB expression in MEKK1-/- cells forms an inhibitory AP-1 complex that binds to the uPA promoter and inhibits uPA transcription. MEKK1 also regulates Fra-2 protein stability by inducing Fra-2 ubiquitination and degradation. MEKK1 regulates AP-1-dependent gene expression by regulating the expression, activity and degradation of component members of the AP-1 complex. Controlling the repertoire of a transcription factor complex is a newly defined function for an MAPK kinase kinase.
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Text Mining Data
FGF-2 → AP-1: "
Both
FGF-2 and phorbol ester-inducible urokinase-type plasminogen activator ( uPA ) expression
requires AP-1 binding to an enhancer element in the uPA promoter, and we have previously shown that FGF-2 or PMA induction of uPA expression is strongly dependent on MEKK1
"
FGF-2 → MEKK1: "
Both FGF-2 and phorbol ester-inducible urokinase-type plasminogen activator ( uPA ) expression requires AP-1 binding to an enhancer element in the uPA promoter, and we have previously shown that FGF-2 or PMA induction of uPA expression is strongly dependent on MEKK1
"
AP-1 → plasminogen: "
Both FGF-2 and phorbol ester-inducible urokinase-type plasminogen activator ( uPA ) expression requires AP-1 binding to an enhancer element in the uPA promoter, and we have previously shown that FGF-2 or PMA induction of uPA expression is strongly dependent on MEKK1
"
uPA → FGF-2: "
Both FGF-2 and phorbol ester-inducible urokinase-type plasminogen activator ( uPA ) expression requires AP-1 binding to an enhancer element in the uPA promoter, and we have previously shown that FGF-2 or PMA induction of uPA expression is strongly dependent on MEKK1
"
uPA → MEKK1: "
Both FGF-2 and phorbol ester-inducible urokinase-type plasminogen activator ( uPA ) expression requires AP-1 binding to an enhancer element in the uPA promoter, and we have previously shown that FGF-2 or PMA induction of uPA expression is strongly dependent on MEKK1
"
AP-1 complex ⊣ uPA: "
Upregulation of JunB expression in MEKK1-/- cells forms an inhibitory AP-1 complex that binds to the uPA promoter and inhibits uPA transcription
"
uPA ⊣ JunB: "
Upregulation of JunB expression in MEKK1-/- cells forms an inhibitory AP-1 complex that binds to the uPA promoter and inhibits uPA transcription
"
Fra-2 → MEKK1: "
MEKK1 also regulates Fra-2 protein stability by inducing Fra-2 ubiquitination and degradation
"
Manually curated Databases
-
IRef Biogrid Interaction:
FOSL2
—
UBC
(physical association, affinity chromatography technology)
In total, 1 gene pairs are associated to this article in curated databases