Metastasis suppressor function of NM23-H1 requires its 3'-5' exonuclease activity.

ABSTRACT: The metastasis suppressor NM23-H1 possesses 3 enzymatic activities in vitro, a nucleoside diphosphate kinase (NDPK), a protein histidine kinase and a more recently characterized 3'-5' exonuclease. Although the histidine kinase has been implicated in suppression of motility in breast carcinoma cell lines, potential relevance of the NDPK and 3'-5' exonuclease to metastasis suppressor function has not been addressed in detail. To this end, site-directed mutagenesis and biochemical analyses of bacterially expressed mutant NM23-H1 proteins have identified mutations that disrupt the 3'-5' exonuclease alone (Glu(5) to Ala, or E(5) A), the NDPK and histidine kinase activities tandemly (Y(52) A, H(118) F) or all 3 activities simultaneously (K(12) Q). Although forced expression of NM23-H1 potently s

SUBMITTER: Zhang Q 

PROVIDER: S-EPMC2946830 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature