Cotranslation of activated mutant p53 with wild type drives the wild-type p53 protein into the mutant conformation

J Milner, EA Medcalf - Cell, 1991 - cell.com
J Milner, EA Medcalf
Cell, 1991cell.com
Activating mutations of~ 53 promote tumor progression. The mutant protein adopts a
characteristic conformation, which lacks the growth suppressor function of wild-type~ 53. We
show that. inutant~ 53 can drive cotranslated wild-type~ 53 into the mutant conformation: a
similar effect in vivo would block wildtype suppressor function with dominant negative effect.
The cotranslatlonal effect of mutant~ 53 on wild-type conformation depends upon interaction
between nascent polypeptides and oligomerlratlon of the full-length proteins. We also show …
Summary
Activating mutations of~ 53 promote tumor progression. The mutant protein adopts a characteristic conformation, which lacks the growth suppressor function of wild-type~ 53. We show that. inutant~ 53 can drive cotranslated wild-type~ 53 into the mutant conformation: a similar effect in vivo would block wildtype suppressor function with dominant negative effect. The cotranslatlonal effect of mutant~ 53 on wild-type conformation depends upon interaction between nascent polypeptides and oligomerlratlon of the full-length proteins. We also show that oligomers of~ 53 proteins can be induced to change conformation in a cooperative manner. Cell growth stimulation induces a similar conformational change in~ 53, and our present results indicate that this may involve allosteric regulation.
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