BBA - Reviews on Cancer (v.1470, #1)

Heterochromatin function in complex genomes by Steven Henikoff (O1-O8).
Keywords: Heterochromatin; Position-effect variegation; Satellite sequence; Transposon; Centromere;

Keywords: Kinase; Phosphatase; Receptor; Adaptor; Mitogenesis; Cell adhesion; Signaling pathway;

The Keystone Symposium on the Molecular Basis of Cancer was an excellent meeting, which stimulated the exchange of a great deal of information. This report was prepared to organize some of the results that provided new insights into the regulation of cell proliferation and apoptosis. We were unable to report on all of the talks and posters due mostly to our limited capacity to absorb and digest the large amount of results presented at the meeting. We apologize to those whose results were not covered in this report.

The E2F transcription factors: key regulators of cell proliferation by Heiko Müller; Kristian Helin (M1-M12).
Ever since its discovery, the RB-1 gene and the corresponding protein, pRB, have been a focal point of cancer research. The isolation of E2F transcription factors provided the key to our current understanding of RB-1 function in the regulation of the cell cycle and in tumor suppression. It is becoming more and more evident that the regulatory circuits governing the cell cycle are very complex and highly interlinked. Certain aspects of RB-1 function, for instance its role in differentiation, cannot be easily explained by the current models of pRB–E2F interaction. One reason is that pRB has targets different from E2F, molecules like MyoD for instance. Another reason may be that we have not completely understood the full complexity of E2F function, itself. In this review, we will try to illuminate the role of E2F in pRB- and p53-mediated tumor suppression pathways with particular emphasis on the aspect of E2F-mediated transcriptional regulation. We conclude that E2F can mediate transcriptional activation as well as transcriptional repression of E2F target genes. The net effect of E2F on the transcriptional activity of a particular gene may be the result of as yet poorly understood protein–protein interactions of E2F with other components of the transcriptional machinery, as well as it may reflect the readout of the different ways of regulating E2F activity, itself. We will discuss the relevance of a thorough understanding of E2F function for cancer therapy.
Keywords: E2F; Cell proliferation; Cell cycle; pRB; p53; Transactivator; Transcription; Tumor suppressor;

Keywords: TGF-β; Colon cancer; DNA repair; Methylation;