Identification of the tumor metastasis suppressor Nm23-H1/Nm23-R1 as a constituent of the centrosome

Processes like cell proliferation, differentiation, and tumor metastasis re quire a flexible adaptation of cell shape and cell plasticity. A regulator of cell structure and shape is the centrosome and its associated microtubul es. Recently, oncogenes like p53, pRB, and the tumor suppressor BRCA1 have been characterized as members of the centrosome. In this communication, we identified rat Nm23-R1/NDPK beta, a homologue of the human tumor metastasis suppressor Nm23-H1 and a regulator of cell proliferation and differentiati on, as a component of the centrosomal complex. We used confocal laser scann ing microscopy on different cell types and biochemical analysis of purified centrosomes to demonstrate that Nm23-R1 is located in the centrosome of di viding and nondividing cells. We also showed that the centrosomal enzyme is catalytically active and able to transfer the gamma -phosphate from a nucl eoside triphosphate to a nucleoside diphosphate. In addition, Nm23-R1 coimm unoprecipitated with gamma -tubulin, a core centrosomal protein essential f or microtubule nucleation. In addition, human Nm23R1/-H1 was also shown to be present in the centrosome of different human and rat cell types, demonst rating that the presence of Nm23-H1 homologues in the latter organelle is a general event. (C) 2001 Academic Press.