Oncogenes transcription factors

Fig. 4. Domain structure of mammalian DNA methyltransferases. (a) The domain structure of the known DNA methyltransferases, depicting the conserved catalytic domain (dark box) and other identified domains. Conserved aminoacid motifs in the catalytic domain are shown in lighter shade of gray. (b) Schematic representation of the reported protein-protein interactions of Dnmtl with a number of regulatory proteins interactions that modulate Dnmtl methyitransferase activity (darker rectangles) or mediate methylation-independent transcriptional repression mechanisms (lighter rectangles). When Dnmtl represses transcription through its enzymatic activity, it has been described to interact with some proteins PCNA [37] and an oncogenic transcription factor PML-RAR [25]. Note that in the case of the PML-RAR transcription factor, histone deacetylase 1 (HDACl) is also bound to the complex. When Dnmtl represses transcription via methylation-independent pathways, it binds to HDACs either directly [34] or indirectly through other proteins the corepressor DMAPl [33], the retinoblastoma protein, and a gene-specific transcription factor [31].

Di Croce, L. et al. (2002) Methyltransferase recruitment and DNA hypermethylation of target promoters by an oncogenic transcription factor. Science, 295, 1079-1082. 

Look, A.T. Oncogenic transcription factors in the human acute leukemias (1997) Science 278, 1059-1064... 

Fig. 5.12 Dehydron pattern of oncogenic transcription factor jun/fos (tetramer, PDB.1FOS). Intermolecular wrapping is displayed as in Fig. 5.10. Monomeric jun chains are in blue and fos chains in dark red. Reprinted with permission from [19] copyright 2007 American Chemical Society...

Zwemer JP, Joo J, Warner KL, et al. The EWS/FLIl oncogenic transcription factor der ulates GLIl. Oncogene. 2008 27 3282-3291. 

The subsequent articles take up such matters as origins, genetic testing for risk, detection by nucleic-based acid methods, oncogene transcription factors, genetic approaches in the discovery of anticancer drags, environment and cancer, and chrano-prevention. 

Fig. 18.5. Phosphorylation cascade leading to activation of proto-oncogene transcription factors myc, fos, and jun.

Look A (1997) Oncogenic transcription factors in the human acute leukemias. Science 21S 1059-1064 Rabbitts TH (1994) Chromsomal translocations in human cancer. Nature 372 143-149 Orphanides G, Lagrange T, Reinberg D (1996) The general transcription factors of RNA polymerase II. Gene Develop 10 2657-2683... 

The leucine zipper motif (see Chapter 3) was first recognized in the amino acid sequences of a yeast transcription factor GCN4, the mammalian transcription factor C/EBP, and three oncogene products, Fos, Jun and Myc, which also act as transcription factors. When the sequences of these proteins are plotted on a helical wheel, a remarkable pattern of leucine residues... 

A considerable number of transcription factors have reactive cysteine residues, which enable them to respond to the redox conditions in the cell. Since cadmium perturbs redox homeostasis, it can affect this class of transcription factors. If cadmium can displace the tetra-coordinate zinc atoms in zinc finger-containing transcription factors, it will affect them as well. Many of the pathways involving activation and inactivation of transcription factors involve kinases and phosphatases, themselves under the intricate control of calcium fluxes. It is therefore no surprise that cadmium will exert effects on the activity of transcription factors, the activation of proto-oncogenes, and thereby on gene expression (Figure 20.8i and i ). 

Transcription regulators are also known to be sumoylated. One of tbe early studies of tbis phenomenon showed that promyelocytic leukemia protein (PML) is a substrate for SUMO conjugation. Once SUMO is attached to the PML protein it is directed to a subdomain of tbe nucleus called tbe PML oncogenic domain (POD). It is thought that POD localization of the PML protein allows it to recruit other proteins such as transcription factors. Transcription factors in the POD can activate or inhibit transcription. Another transcription factor known to be sumoylated is Sp3. ° SUMO also has roles in chromatin condensation and interphase chromosome organization. ... 

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