The passage of mammalian cells through the restriction point into the
S phase of the cell cycle is regulated by the activities of Cdk4 and C
dk6 complexed with the D-type cyclins and by cyclin E/Cdk2 (refs 1-3).
The activities of these holoenzymes are constrained by CDK inhibitory
proteins(4,5). The importance of the restriction point is illustrated
by its deregulation in many tumour cells(6,7) and upon infection with
DNA tumour viruses(8). Here we describe the properties of cyclins enc
oded by two herpesviruses, herpesvirus saimiri (HVS) which can transfo
rm blood lymphocytes(9) and induce malignancies of lymphoid origin in
New World primates(9,10) and human herpesvirus 8 (HHV8) implicated as
a causative agent of Kaposi's sarcoma and body cavity lymphomas(11,12)
. Both viral cyclins form active kinase complexes with Cdk6 that are r
esistant to inhibition by the CDK inhibitors p16(Ink4a), p21(Cip1) and
p27(Kip1). Furthermore, ectopic expression of a viral cyclin prevents
G1 arrest imposed by each inhibitor and stimulates cell-cycle progres
sion in quiescent fibroblasts. These results suggest a new mechanism f
or deregulation of the cell cycle and indicate that the viral cyclins
may contribute to the oncogenic nature of these viruses.