Phosphorylation of human MAD1 by the BUB1 kinase in vitro.
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.
Seeley
T W
TW
Chiron Corporation, 4560 Horton Street, Emeryville, California, 94608, USA.
Wang
L
L
Zhen
J Y
JY
D048868:Adaptor Proteins, Signal Transducing; D000255:Adenosine Triphosphate / Q000378:metabolism; D019943:Amino Acid Substitution; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000494:pharmacology; D018797:Cell Cycle Proteins; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008239:Lysine / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D034521:Nuclear Matrix-Associated Proteins; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D029543:Nucleocytoplasmic Transport Proteins; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D000075223:Poly-ADP-Ribose Binding Proteins; D011233:Precipitin Tests; D011485:Protein Binding; D014176:Protein Biosynthesis; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins
D048868:Adaptor Proteins, Signal Transducing; C489444:BUB3 protein, human; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D005656:Fungal Proteins; D047908:Intracellular Signaling Peptides and Proteins; C501384:MAD1L1 protein, human; D034521:Nuclear Matrix-Associated Proteins; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D010750:Phosphoproteins; D000075223:Poly-ADP-Ribose Binding Proteins; D047428:Protein Kinase Inhibitors; D011506:Proteins; C490522:RAE1 protein, human; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C015482:protein kinase modulator; D000255:Adenosine Triphosphate; D011494:Protein Kinases; C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases; D008239:Lysine