Colin W. Garvie

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Activation of p53 tumor suppressor by antagonizing its negative regulator murine double minute (MDM)2 has been considered an attractive strategy for cancer therapy and several classes of p53-MDM2 binding inhibitors have been developed. However, these compounds do not inhibit the p53-MDMX interaction, and their effectiveness can be compromised in tumors(More)
Pax5 regulates the B cell-specific expression of the mb-1 gene together with members of the Ets family of transcriptional activators. The Ets proteins on their own bind poorly to the Pax5/Ets binding site, but can be recruited to the site by cooperative interactions with Pax5. The structure of the ETS domain of Ets-1 and the paired domain of Pax5 bound to(More)
The DNA-binding activity of the eukaryotic transcription factor Ets-1 (E26 avian erythroblastosis virus oncogene-E twenty-six) is negatively regulated by inhibitory regions that flank the ETS domain. Based on the results of solution studies, these N- and C-terminal inhibitory regions have been proposed to pack against the ETS domain and form an(More)
Pax-5, a member of the paired domain family of transcription factors, is a key regulator of B lymphocyte-specific transcription and differentiation. A major target of Pax-5-mediated activation is the mb-1 gene, which encodes the essential transmembrane signaling protein Ig-alpha. Pax-5 recruits three members of the Ets family of transcription factors:(More)
RNase L is part of the innate immune response to viral infection. It is activated by a small oligonucleotide (2-5A) whose synthesis is initiated as part of the interferon response. Binding of 2-5A to the N-terminal regulatory region, the ANK domain, of RNase L activates its ribonuclease activity and results in cleavage of RNA in the cell, which ultimately(More)
We present the results of in vitro DNA-binding assays for a mutant protein (Q44K) of the E. coli methionine repressor, MetJ, as well as the crystal structure at 2.2 A resolution of the apo-mutant bound to a 10-mer oligonucleotide encompassing an 8 bp met-box sequence. The wild-type protein binds natural operators co-operatively with respect to protein(More)
Pax5 (paired box binding factor 5) is a critical regulator of transcription and lineage commitment in B lymphocytes. In B cells, mb-1 (Ig-alpha/immunoglobulin-associated alpha) promoter transcription is activated by Pax5 through its recruitment of E74-like transforming sequence (Ets) family proteins to a composite site, the P5-EBS (Pax5-Ets binding site).(More)
BACKGROUND The methionine repressor, MetJ, represses the transcription of genes involved in methionine biosynthesis by binding to arrays of two to five adjacent copies of an eight base-pair 'metbox' sequence. Naturally occurring operators differ from the consensus sequence to a greater extent as the number of metboxes increases. MetJ, while accommodating(More)