The model organism Saccharomyces cerevisiae is providing new insights into the molecular and cellular changes that are related to aging. The yeast protein Sir2p (Silent Information Regulator 2) is a histone deacetylase involved in transcriptional silencing and the control of genomic stability. Recent results have led to the identification of Sir2p as a crucial determinant of yeast life span. Dosage, intracellular localization, and activity of Sir2p all have important effects on yeast longevity. For instance, calorie restriction apparently increases yeast life (...) span by increasing Sir2p activity. Since Sir2p‐related proteins have been identified in many prokaryotic and eukaryotic organisms, the fundamental principles derived from the studies in yeast may prove valuable in directing our future research toward an understanding of the mechanisms of aging in higher eukaryotes. BioEssays 23:327–332, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

CpG islands (CGIs) are regions enriched in the dinucleotide CpG; they constitute the promoter of about 60% of mammalian genes. In cancer cells, some promoter‐associated CGIs become heavily methylated on cytosines, and the corresponding genes undergo stable transcriptional silencing. Hypermethylated CGIs attract methyl‐CpG‐binding proteins (MBPs), which have been shown to recruit chromatin modifiers and cause transcriptional repression. These observations have led to the prevalent model that methyl‐CpG‐binding proteins are promoter‐proximal transcriptional repressors. Recent discoveries challenge this idea and raise a number (...) of questions. Here we discuss the following issues: what are other possible roles for the known MBPs? Why are these proteins not essential in mammals? Are there other MBPs left to discover? Could CpG methylation be nonessential? (shrink)

The BTB domain is a protein–protein interaction motif that is found throughout eukaryotes. It determines a unique tri‐dimensional fold with a large interaction surface. The exposed residues are highly variable and can permit dimerization and oligomerization, as well as interaction with a number of other proteins. BTB‐containing proteins are numerous and control cellular processes that range from actin dynamics to cell‐cycle regulation. Here, we review findings in the field of transcriptional regulation to illustrate how the high variability of the BTB (...) has allowed related transcription factors to evolve different functional abilities. We then report how recent work has showed that, in spite of their high sequence divergence and apparently unrelated functions, many BTB‐containing proteins have at least one shared role: the recruitment of degradation targets to E3 ubiquitin ligase complexes. Taken together, these findings illustrate diverse and convergent functions of a versatile protein–protein interaction domain. BioEssays 28: 1194–1202, 2006. © 2006 Wiley Periodicals, Inc. (shrink)