Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51812 (mitogen-activated protein)
 10,636 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Collagenase-1 (matrix metalloproteinase-1 (MMP-1)) degrades the extracellular matrix and enhances the invasive phenotype of tumor cells. v-src activated MMP-1 transcription through a series of elements in the proximal promoter, including the E2BP (nt -172), polyoma virus enhancer A3 (PEA3) (nt -94), activator protein-1 (AP-1) (nt -72), and signal transducer and activator of transcription (STAT) (nt -57) consensus sites. Of these sites, PEA3 and STAT contributed specifically to induction by v-src, whereas the remaining elements were also involved in induction by the phorbol ester phorbol myristate acetate (PMA). However, in contrast to MMP-1 induction by PMA, an AP-1 site located at nt -186 did not contribute to v-src induction. These results suggest divergence of the tyrosine kinase- and protein kinase C-dependent pathways with respect to MMP-1 transcription. v-src induced MMP-1 through mitogen-activated protein kinases, with extracellular signal-regulated kinases playing a larger role than c-jun N-terminal kinase. Retinoic acid, which inhibits the progression of certain cancers, repressed v-src-induced MMP-1 transcription. Constitutive expression of retinoic acid receptors (RARs) alpha or beta, but not gamma, or of retinoid X receptor alpha, repressed v-src-induced collagenase-1 transcription. We concluded that oncogenic induction of MMP-1 by v-src depends on signaling pathways and cis-acting sequences that are distinct from those involved in phorbol ester activation. Furthermore, v-src induction of MMP-1 may, by acting in concert with other genes, enhance matrix degradation and tumor progression, and retinoic acid and RARs may antagonize this induction in an RAR type-specific manner.
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PMID:v-src activation of the collagenase-1 (matrix metalloproteinase-1) promoter through PEA3 and STAT: requirement of extracellular signal-regulated kinases and inhibition by retinoic acid receptors. 953 51

Monocyte extravasation initiates reorganization of the cytoskeleton (CSK) and adhesion-dependent cytokine gene transcription. The actin CSK is thought to be crucial for compartmentalization and translation of mRNA, many of which contain AU-rich (ARE) instability motifs in the 3' untranslated region. We investigated regulation of adhesion-induced IL-1 beta expression by the monocyte CSK. In serum-free adherent monocytes, the induced IL-1 beta mRNA was stable and did not coextract with actin filaments. In contrast, in cells adherent in autologous serum, IL-1 beta transcripts were unstable, coextracted with actin filaments and were associated with only transient activation of the mitogen-activated protein kinases (MAPK). Under both conditions of adherence, the ARE-binding protein AUF1/hnRNP D was readily extracted in the cytosolic fraction. Electro-injection with AUF1/hnRNP D modified the actin CSK and, surprisingly, stabilized IL-1 beta transcripts. These data suggest that the control of mRNA degradation is linked with changes in the CSK. Mitogen-activated protein kinase activation or alterations in the availability of mRNA degradation factors may mediate these effects.
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PMID:IL-1 beta transcript stability in monocytes is linked to cytoskeletal reorganization and the availability of mRNA degradation factors. 1212 Dec 21