Inhibitors of protein kinase C (PKC) prevent activated transcription - Role of events downstream of NF-kappa B DNA binding
UNSPECIFIED. (2004) Inhibitors of protein kinase C (PKC) prevent activated transcription - Role of events downstream of NF-kappa B DNA binding. JOURNAL OF BIOLOGICAL CHEMISTRY, 279 (18). pp. 18457-18466. ISSN 0021-9258Full text not available from this repository.
Official URL: http://dx.doi.org/10.1074/jbc.M400765200
In pulmonary A549 cells, the protein kinase C (PKC) inhibitor, Ro 31-8220, and the phosphotidylcholine-specific phospholipase C inhibitor, D609, prevent NF-kappaB-dependent transcription, yet NF-kappaB DNA binding is unaffected (Bergmann, M., Hart, L., Lindsay, M., Barnes, P. J., and Newton, R. (1998) J. Biol. Chem. 273, 6607-6610). We now show that this effect also occurs in BEAS-2B bronchial epithelial cells as well as with other PKC inhibitors (G? 6976, GF109203X, and calphostin C) in A549 cells. Similarly, phorbol ester, a diacylglycerol mimetic, activates NF-kappaB-dependent transcription and potentiates tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB-dependent transcription, yet unlike TNFalpha, poorly activates IkappaB kinase (IKK) activity, IkappaBalpha degradation, or NF-kappaB DNA binding in both A549 and BEAS-2B cells. As phorbol ester-induced NF-kappaB-dependent transcription was relatively insensitive to the proteasome inhibitor, MG-132, PKC may affect NF-kappaB-dependent transcription via mechanisms other than the core IKK-IkappaB pathway. This is supported by Gal4 one hybrid analysis of p65/RelA transactivation, which was potentiated by TNFalpha and phorbol ester and was inhibited by Ro 31-8220 and D609. Additionally, a number of PKC isoforms, particularly the novel isoform PKCepsilon, induced p65/RelA transactivation. Phosphorylation of p65/RelA and cAMP-responsive element-binding protein (CREB)-binding protein (CBP) was increased by TNFalpha treatment and, in the case of CBP, was prevented by Ro 31-8220 or D609. However, p65/RelA-CBP interactions were unaffected by either compound. As this effect was not limited to NF-kappaB, but was a more general feature of inducible gene transcription, we suggest PKC isoforms may provide a point of intervention in diseases such as inflammation, or cancer, where activated gene expression is prominent.
|Item Type:||Journal Article|
|Subjects:||Q Science > QD Chemistry|
|Journal or Publication Title:||JOURNAL OF BIOLOGICAL CHEMISTRY|
|Publisher:||AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC|
|Official Date:||30 April 2004|
|Number of Pages:||10|
|Page Range:||pp. 18457-18466|
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