Virus-encoded cyclin.
Herpesvirus saimiri contains an open reading frame called eclf2 with homology to the cellular type D cyclins. We now show that the eclf2 gene product is a novel virus-encoded cyclin (v-cyclin). The protein encoded by the v-cyclin gene of this oncogenic herpesvirus was found to have an apparent molecular size of 29 kDa in transformed cells. v-Cyclin protein was found to be associated with cdk6, a cellular cyclin-dependent kinase known to interact with cellular type D cyclins. cdk6/v-cyclin complexes strongly phosphorylated Rb fusion protein and histone H1 as substrates in vitro. Mutational analyses showed that highly conserved amino acids in the cyclin box of v-cyclin were important for association with cdk6 and for activation of cdk6 kinase activity. Thus, v-cyclin resembles cellular type D cyclins in primary sequence, in its association with cdk6, by its ability to activate protein kinase activity, and by the presence of functional cyclin box sequences. v-Cyclin exhibited a selective preference for association with cdk6 over other cyclin-dependent kinases and a high level of kinase activation. The properties of v-cyclin suggest a likely role in oncogenic transformation by this T-lymphotropic herpesvirus.
Jung
J U
JU
New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772-9102.
Stäger
M
M
Desrosiers
R C
RC
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D017124:Conserved Sequence; D051361:Cyclin-Dependent Kinase 6; D018844:Cyclin-Dependent Kinases; D016213:Cyclins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D005814:Genes, Viral; D006567:Herpesvirus 2, Saimiriine / Q000235:genetics*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009036:Moths; D009154:Mutation; D016366:Open Reading Frames; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism
D016213:Cyclins; D017931:DNA Primers; D004279:DNA, Viral; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D051361:Cyclin-Dependent Kinase 6; D018844:Cyclin-Dependent Kinases