Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.16.2 (tyrosine hydroxylase)
 14,760 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypoxia is an important pathophysiological stress that occurs during blood vessel injuries and tumor growth. It is now well documented that hypoxia leads to the activation of several transcription factors which participate in the adaptive response of the cells to hypoxia. Among these transcription factors, AP-1 is rapidly activated by hypoxia and triggers bFGF, VEGF, and tyrosine hydroxylase gene expression. However, the mechanisms of AP-1 activation by hypoxia are not well understood. In this report, we studied the events leading to AP-1 activation in hypoxia. We found that c-jun protein accumulates in hypoxic HepG2 cells. This overexpression is concomitant with c-jun phosphorylation and JNK activation. Moreover, we showed that AP-1 is transcriptionally active. We also observed that AP-1 transcriptional activity is inhibited by a MEKK1 dominant negative mutant. Moreover, the MEKK1 dominant negative mutant as well as deletion of the AP-1 binding sites within the c-jun promoter inhibited the c-jun promoter activation by hypoxia. All together, these results indicate that, in hypoxic HepG2 cells, AP-1 is activated through a JNK-dependent pathway and that it is involved in the regulation of the c-jun promoter, inducing a positive feedback loop on AP-1 activation via c-jun overexpression.
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PMID:c-JUN gene induction and AP-1 activity is regulated by a JNK-dependent pathway in hypoxic HepG2 cells. 1128 49

p53 is a transcription factor and then induced by cellular stress regulates ageing, cell cycle arrest and apoptosis. Published data also demonstrated that p53 participates in the regulation of neuronal differentiation. However, the data concerning the mechanisms of neuronal differentiation by p53 is very limited. In the present work we have studied a role and mechanisms of p53 activated by Nutlin-3 in the differentiation of PC12 cells. In our experiments Nutlin-3 stimulated the cell differentiation by significantly increasing of the neuritis upgrowth and upregulation of tyrosine hydroxylase (TH) expression, the catecholamine main rate-limited ferment. We have also analyzed MAPK signaling cascade that tightly participate in the neuronal differentiation. Obtained data demonstrated that activation of p53 by Nutlin-3 injections increased the activity of cRaf and ERK1/2, as well as transcription factor CREB, which is one of the targets for ERK pathway and regulates transcription of TH. Thus, we demonstrated that p53 activation lead to increased differentiation of PC12 cells and this effect is mediated by cRaf/ERK/CREB pathway.
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PMID:[Role p53 and MAPK signaling integration in the regulation of PC12 cell neural differentiation]. 2593 82