Boguski Signaling Structural Regulatory Structural Biology

markboguski.net

Home Education Employment Publications Presentations Boards Teaching Awards

Signaling & Structural Biology

The A20 cDNA Induced by Tumor Necrosis Factor Alpha Encodes a Novel Type of Zinc Finger Protein (1990) |PubMed|PDF|
The NF1 Locus Encodes a Protein Functionally Related to Mammalian GAP and Yeast Ira Proteins (1990) |PubMed|PDF|
A Repeating Amino Acid Motif in CDC23 Defines a Family of Proteins and a New Relationship among Genes Required for Mitosis and RNA Synthesis (1990) |PubMed|PDF|
Structure and Evolution of a Human Erythroid Transcription Factor (1990) |PubMed|PDF|
sar1, a Gene from Schizosaccharomyces pombe Encoding a Protein That Regulates ras1 (1991) |PubMed|PDF|
TPR Proteins as Essential Components of the Yeast Cell Cycle (1991) |PubMed|PDF|
Analysis of Conserved Domains and Sequence Motifs in Cellular Regulatory Proteins and Locus Control Regions Using New Software Tools for Multiple Alignment and Visualization (1992) |PubMed|PDF|
Novel Repetitive Sequence Motifs in the Alpha and Beta Subunits of Prenyl-Protein Transferases and Homology of the Alpha Subunit to the Mad2 Gene Product of Yeast (1992) |PubMed|PDF|
Proto-Vav and Gene Expression (1992) |PubMed|PDF|
Influence of Guanine Nucleotides on Complex Formation between Ras and Cdc25 Proteins (1993) |PubMed|PDF|
Proteins Regulating Ras and Its Relatives (1993) |PubMed|PDF| In 1990, I made the startling observation that the product of the recently-cloned human gene for type 1 Neurofibromatosis (NF1) was probably a GTPase-activating protein (GAP) and therefore that the underlying pathophysiology of neurofibromatosis involved aberrant regulation of the ras pathway. This functional prediction was made on the basis of database searching and sequence alignments that showed NF1 to be evolutionarily-related (homologous) to two yeast genes, IRA1 and IRA2. Complementation experiments in ira1^- and ira2^- mutants proved that NF1 encoded a functional equivalent of rasGAP in yeast (Ballester et al., 1990). This demonstration of the potential power of computational biology and comparative (yeast-human) genomics led to my interest in cytoplasmic signal transduction proteins (including vav, rab escort proteins and guanine nucleotide dissociation inhibitors and protein prenyltransferases) which I worked on for a number of years. The domain complexity of many of these proteins necessitated the development of new algorithms and software tools for multiple sequence alignment and visualization (Boguski et al., 1992). This paper published in 1993, although labeled by Nature as a review article, was actually a hybrid publication that contained a great deal of new analyses (multiple sequence alignments) of numerous and multiform proteins containing interaction and/or adapter domains which Frank McCormick and I hypothesized “…may serve to interconnect different regulatory pathways.” Data and results in this paper served as a framework to organize and synthesize large amounts of biochemical and genetic data on ras-mediated signal transduction from experiments in a variety of organisms. For the first time, we also comprehensively identified gene and protein sequences by explicit reference to database accession numbers thereby making it much easier for others to reproduce and build upon our work.
A Novel Ring Finger Protein Interacts with the Cytoplasmic Domain of CD40 (1994) |PubMed|PDF|
Threading Analysis Suggests That the Obese Gene Product May Be a Helical Cytokine (1995) |PubMed |PDF| Our results were surprising because, up until that point, no one thought that fat metabolism would be in any way related to cytokine signaling pathways. Indeed, our paper was originally rejected by another journal because the reviewers were incredulous about the regulatory pathways our structure implied.
Evolutionary Conservation and Somatic Mutation Hotspot Maps of p53: Correlation with p53 Protein Structural and Functional Features (1999) |PubMed|PDF|

Home Education Employment Publications Presentations Boards Teaching Awards

Tom Madej, Steve Bryant and I accurately predicted, by computational biology alone, the 3-D structure of the protein encoded by a mouse "obesity" gene (leptin) cloned by Jeff Friedman in 1995. Our prediction was confirmed by both NMR and crystal structures published two years later.