The human kinesin-like protein RB6K is under tight cell cycle control and is essential for cytokinesis

Several members of the kinesin superfamily are known to play a prominent ro le in the motor-driven transport processes that occur in mitotic cells. Her e we describe a new mitotic human kinesin-like protein, RB6K (Rabkinesin 6) , distantly related to MKLP-1. Expression of RB6K is regulated during the c ell cycle at both the mRNA and protein level and, similar to cyclin B, show s a maximum during M phase. Isolation or the RB6K promoter allowed identifi cation of a CDE-CHR element and promoter activity was shown to be maximal d uring M phase. Immunofluorescence microscopy using antibodies raised agains t RB6K showed a weak signal in interphase Golgi but a 10-fold higher signal in prophase nuclei. During M phase, the newly synthesized RB6K does not co localise with Rab6. In later stages of mitosis RB6K localized to the spindl e midzone and appeared on the midbodies during cytokinesis, The functional significance of this localization during M phase was revealed by antibody m icroinjection studies which resulted exclusively in binucleate cells, showi ng a complete failure of cytokinesis. These results substantiate a crucial role for RB6K in late anaphase B and/or cytokinesis, clearly distinct from the role of MKLP-1.