Identification of the tumor metastasis suppressor Nm23-H1/Nm23-R1 as a constituent of the centrosome.
Processes like cell proliferation, differentiation, and tumor metastasis require a flexible adaptation of cell shape and cell plasticity. A regulator of cell structure and shape is the centrosome and its associated microtubules. 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/NDPKbeta, a homologue of the human tumor metastasis suppressor Nm23-H1 and a regulator of cell proliferation and differentiation, as a component of the centrosomal complex. We used confocal laser scanning microscopy on different cell types and biochemical analysis of purified centrosomes to demonstrate that Nm23-R1 is located in the centrosome of dividing and nondividing cells. We also showed that the centrosomal enzyme is catalytically active and able to transfer the gamma-phosphate from a nucleoside triphosphate to a nucleoside diphosphate. In addition, Nm23-R1 coimmunoprecipitated with gamma-tubulin, a core centrosomal protein essential for microtubule nucleation. In addition, human Nm23-R1/-H1 was also shown to be present in the centrosome of different human and rat cell types, demonstrating that the presence of Nm23-H1 homologues in the latter organelle is a general event.
Roymans
D
D
Cellular Biochemistry, University of Antwerp, Wilrijk-Antwerpen, B-2610, Belgium.
Vissenberg
K
K
De Jonghe
C
C
Willems
R
R
Engler
G
G
Kimura
N
N
Grobben
B
B
Claes
P
P
Verbelen
J P
JP
Van Broeckhoven
C
C
Slegers
H
H
D000255:Adenosine Triphosphate / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D018385:Centrosome / Q000737:chemistry / Q000378:metabolism*; D005910:Glioma / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000096:biosynthesis; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D020559:Monomeric GTP-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D054778:NM23 Nucleoside Diphosphate Kinases; D009362:Neoplasm Metastasis; D009701:Nucleoside-Diphosphate Kinase / Q000032:analysis / Q000378:metabolism*; D011233:Precipitin Tests; D051381:Rats; D011994:Recombinant Proteins / Q000032:analysis / Q000378:metabolism; D014157:Transcription Factors / Q000032:analysis / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1; D014404:Tubulin / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D007527:Isoenzymes; D054778:NM23 Nucleoside Diphosphate Kinases; D011994:Recombinant Proteins; C508960:TGFB1 protein, human; C508962:Tgfb1 protein, rat; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014404:Tubulin; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins