http://aiocm.org/member/Immunity,%20Inflammation,%20and%20Cancer.pdf

Immunity, Inflammation, and Cancer

The glutathione S-transferases (GST) represent a major group of detoxification enzymes. All eukaryotic species possess multiple cytosolic and membrane-bound GST isoenzymes, each of which displays distinct catalytic as well as noncatalytic binding properties: the cytosolic enzymes are encoded by at least five distantly related gene families (designated class alpha, mu, pi, sigma, and theta GST), whereas the membrane-bound enzymes, microsomal GST and leukotriene C, synthetase, are encoded by single genes and both have arisen separately from the soluble GST. Evidence suggests that the level of expression of GST is a crucial factor in determining the sensitivity of cells to a broad spectrum of toxic chemicals. In this article the biochemical functions of GST are described to show how individual isoenzymes contribute to resistance to carcinogens, antitumor drugs, environmental pollutants, and products of oxidative stress.A description of the mechanisms of transcriptional and posttranscriptional regulat...

The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance.

The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation.

Matrix metalloproteinases (MMPs) are a family of nine or more highly homologous Zn(++)-endopeptidases that collectively cleave most if not all of the constituents of the extracellular matrix. The present review discusses in detail the primary structures and the overlapping yet distinct substrate specificities of MMPs as well as the mode of activation of the unique MMP precursors. The regulation of MMP activity at the transcriptional level and at the extracellular level (precursor activation, inhibition of activated, mature enzymes) is also discussed. A final segment of the review details the current knowledge of the involvement of MMP in specific developmental or pathological conditions, including human periodontal diseases.

Matrix Metalloproteinases: A Review

The cloning of genes encoding mammalian DNA binding transcription factors for RNA polymerase II has provided the opportunity to analyze the structure and function of these proteins. This review summarizes recent studies that define structural domains for DNA binding and transcriptional activation functions in sequence-specific transcription factors. The mechanisms by which these factors may activate transcriptional initiation and by which they may be regulated to achieve differential gene expression are also discussed.

https://science.sciencemag.org/content/sci/245/4916/371.full.pdf

Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins

Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor.

Transcription factor AP-2 mediates induction by two different signal-transduction pathways: protein kinase C and cAMP.

Protein kinase C is important in the transduction of signals generated at the plasma membrane. The physiological activators of protein kinase C are diacylglycerols1, and the tumour-promoting phorbol esters, such as 12-O-tetradecanoyI-phorbol-14 acetate (TPA), constitute another group of specific activators1,2. Many cellular substrates for phosphorylation by protein kinase C have been described1,3, but proteins that directly control transcription in response to protein kinase C activation are yet to be identified. TPA treatment leads to induction of various proto-oncogenes4–7, growth factor genes7,8, and genes encoding secreted proteases9. In addition. TPA increases the activity of viral enhancer elements10–13. To identify trans-acting factors that mediate the transcriptional response to TPA we chose the simian virus 40 (SV40) enhancer14 as a model, because it is known to be composed of several discrete cis-acting elements15–18 which are recognized by multiple trans-acting factors19–21. We report here that the SV40 enhancer contains at least four different TPA responsive elements whose activity is dependent on cell-type. The induction response is likely to involve at least two distinct post-translational steps which modulate the activity of the proteins that recognize these elements.

Masayoshi Imagawa

Papers

Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor.

Transcription factor AP-2 mediates induction by two different signal-transduction pathways: protein kinase C and cAMP.

Multiple cis- and trans-acting elements mediate the transcriptional response to phorbol esters.