Kaposi's sarcoma-associated herpesvirus encodes a functional cyclin.
Kaposi's sarcoma-associated herpesvirus (KSHV) (also called human herpesvirus 8) is consistently found in Kaposi's sarcoma lesions and in body-cavity-based lymphomas. A 17-kb KSHV lambda clone was obtained directly from a Kaposi's sarcoma lesion. DNA sequence analysis of this clone identified an open reading frame which has 32% amino acid identity and 53% similarity to the virus-encoded cyclin (v-cyclin) of herpesvirus saimiri (HVS) and 31% identity and 53% similarity to human cellular cyclin D2. This KSHV open reading frame was shown to encode a 29- to 30-kDa protein with the properties of a v-cyclin. KSHV v-cyclin protein was found to associate predominantly with cdk6, a cellular cyclin-dependent kinase known to interact with cellular type D cyclins and HVS v-cyclin. The KSHV v-cyclin was also found to associate weakly with cdk4. KSHV v-cyclin-cdk6 complexes strongly phosphorylated glutathione S-transferase-Rb fusion protein and histone H1 as substrates in vitro. Thus, KSHV v-cyclin resembles the v-cyclin of the T-lymphocyte-transforming HVS in its specificity for association with cdk6 and in its ability to strongly activate cdk6 protein kinase activity.
Li
M
M
New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772, USA.
Lee
H
H
Yoon
D W
DW
Albrecht
J C
JC
Fleckenstein
B
B
Neipel
F
F
Jung
J U
JU
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002460:Cell Line; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D019288:Herpesvirus 8, Human / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012514:Sarcoma, Kaposi / Q000821:virology*; D017386:Sequence Homology, Amino Acid; D018411:Spodoptera / Q000166:cytology; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
D016213:Cyclins; C118264:HHV8-Vcyc protein, Human herpesvirus 8; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; C495900:CDK4 protein, human; C495911:CDK6 protein, human; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; D018844:Cyclin-Dependent Kinases