IDENTIFICATION OF A NOVEL HUMAN KINESIN-RELATED GENE (HK2) BY THE CDNA DIFFERENTIAL DISPLAY TECHNIQUE

We have used the cDNA differential display technique to isolate genes regulated by the synthetic retinoid N-(4-hydroxyphenyl)-all-trans-reti namide (HPR), a cancer chemopreventive agent in vivo and a powerful in ducer of apoptotic cell death in vitro. Here we report the identificat ion of a novel gene, the expression of which is markedly up regulated in tumor cells after treatment for 30-60 min with HPR. The full-length cDNA of this gene, determined by screening of a human placenta cDNA, is 3.5 kb long and contains an open reading frame of 2037 nt. The gene is >90% homologous to the mouse KIF2, a gene belonging to the family of kinesin-related motor proteins, and we therefore named it HK2 (huma n kinesin 2). A shorter form of the HK2 mRNA (HK2(S)), containing a 57 -nt deletion in the open reading frame, has also been detected. Northe rn analysis revealed that HK2 is widely expressed among hemopoietic an d nonhemopoietic cell lines and tissues. By the use of radiation hybri ds, HK2 has been localized to chromosome 5q12-q13. Kinesins constitute a superfamily of motor proteins that use energy liberated from ATP hy drolysis to move cargo along microtubules and are implicated in mechan isms of mitosis or meiosis. The role of HK2 in the growth-inhibitory a nd apoptotic responses elicited by HPR remains to be established. (C) 1997 Academic Press.