Nm23-H1/NDP kinase folding intermediates and cancer: a hypothesis.

Abstract:

:The Nm23-H1/nucleoside diphosphate (NDP) kinase A is a metastasis suppressor, besides its enzymatic activity. The mutant S120G has been found in high-grade neuroblastomas. The mutant protein, once denatured in urea, is unable to refold in vitro. A size-exclusion chromatography analysis of the folding/association pathway showed that recombinant wild-type and S120G mutant human Nm23-H1/NDP kinase A unfold and refold passing through a molten globule state while typical hexameric NDP kinases unfold without dissociated species and refold through a native monomeric intermediate. A survey of the recent literature showed that several proteins involved in cancer, and their mutants, are marginally stable, like the wild-type Nm23-H1/NDP kinase A, or are misfolded, like its S120G mutant. We therefore suggest that the low thermodynamic stability and the folding intermediate of the Nm23-H1/NDP kinase A may be necessary for its regulatory properties.

journal_name

J Bioenerg Biomembr

authors

Lascu I

doi

10.1007/s10863-006-9042-1

subject

Has Abstract

pub_date

2006-08-01 00:00:00

pages

265-8

issue

3-4

eissn

0145-479X

issn

1573-6881

journal_volume

38

pub_type

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