The BUB/MAD signaling pathway monitors attachment of chromosomes to spindle poles in mitotic cells. Mutations of the human BUB1 locus were identified in cancer cells exhibiting an unstable chromosomal complement. We report that the human BUB3 gene maps to a site on chromosome 10 subject to frequent modification in cancers. Thus, defects in BUB/MAD signaling may contribute to genetic instability and to cancer progression. In vitro, BUB1 and BUB3 proteins form a complex of monomers of each protein. These proteins interact with the human MAD1 gene product, a target of the HTLV-1 tax oncogene. This multiprotein complex exhibits a kinase activity with a requirement for lysine 821 in the BUB1 kinase motif, resulting in BUB1 autophosphorylation and phosphorylation of associated MAD1.
Knowledge representation of the role of phosphorylation is essential for the meaningful understanding of many biological processes. However, such a representation is challenging...
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The structure of Janus kinases (JAKs) is unique among protein tyrosine kinases in having tandem, nonidentical kinase and pseudokinase domains. Despite its conservation in evolut...
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