Abstract
Mad2 participates in spindle checkpoint inhibition of APC(Cdc20). We show that RNAi-mediated suppression of Mad1 function in mammalian cells causes loss of Mad2 kinetochore localization and impairment of the spindle checkpoint. Mad1 and Cdc20 contain Mad2 binding motifs that share a common consensus. We have identified a class of Mad2 binding peptides with a similar consensus. Binding of one of these ligands, MBP1, triggers an extensive rearrangement of the tertiary structure of Mad2. Mad2 also undergoes a similar striking structural change upon binding to a Mad1 or Cdc20 binding motif peptide. Our data suggest that, upon checkpoint activation, Mad1 recruits Mad2 to unattached kinetochores and may promote binding of Mad2 to Cdc20.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Calcium-Binding Proteins / chemistry
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Calcium-Binding Proteins / metabolism*
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Cdc20 Proteins
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Cell Cycle Proteins*
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HeLa Cells
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Humans
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Ligands
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Mad2 Proteins
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Models, Molecular
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Nuclear Proteins / chemistry
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Nuclear Proteins / metabolism
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Phosphoproteins / chemistry
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Phosphoproteins / metabolism*
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Protein Binding
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Protein Conformation
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Proteins / chemistry
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Proteins / metabolism*
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Repressor Proteins / chemistry
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Repressor Proteins / metabolism*
Substances
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Calcium-Binding Proteins
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Cdc20 Proteins
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Cell Cycle Proteins
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Ligands
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MAD1L1 protein, human
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MAD2L1 protein, human
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Mad2 Proteins
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Nuclear Proteins
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Phosphoproteins
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Proteins
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Repressor Proteins
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CDC20 protein, human