Gene interactions and pathways from curated databases and text-mining
Oncogene 2005, PMID: 15558021

MEKK1 regulates the AP-1 dimer repertoire via control of JunB transcription and Fra-2 protein stability.

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