Publication: Gain of function properties of mutant p53 proteins at the mitotic spindle cell cycle checkpoint
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Date
2000
Authors
Hixon, M.L. ; Flores, A. ; Wagner, M. ; Gualberto, A.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Mutations in the p53 tumor suppressor gene
locus predispose human cells to chromosomal instability.
This is due in part to interference of mutant p53 proteins
with the activity of the mitotic spindle and postmitotic
cell cycle checkpoints. Recent data demonstrates that
wild type p53 is required for postmitotic checkpoint
activity, but plays no role at the mitotic spindle
checkpoint. Likewise, structural dominant p53 mutants
demonstrate gain-of-function properties at the mitotic
spindle checkpoint and dominant negative properties at
the postmitotic checkpoint. At mitosis, mutant p53
proteins interfere with the control of the metaphase-toanaphase
progression by up-regulating the expression of
CKsl, a protein that mediates activatory phosphorylation
of the anaphase promoting complex (APC) by Cdc2.
Cells that carry mutant p53 proteins overexpress CKsl
and are unable to sustain APC inactivation and mitotic
arrest. Thus, mutant p53 gain-of-function at mitosis
constitutes a key component to the origin of
chromosomal instability in mutant p53 cells.
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