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Kaposi's sarcoma-associated herpesvirus encodes a functional cyclin
1New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772, USA.
Journal of Virology
|March 1, 1997
Summary
Kaposi's sarcoma-associated herpesvirus (KSHV) encodes a novel viral cyclin (v-cyclin) that binds and activates cellular cyclin-dependent kinase 6 (cdk6). This discovery sheds light on KSHV-driven cellular dysregulation in associated cancers.
Area of Science:
- Oncology
- Virology
- Molecular Biology
Background:
- Kaposi's sarcoma-associated herpesvirus (KSHV), or human herpesvirus 8, is linked to Kaposi's sarcoma and lymphomas.
- Viral cyclins play roles in cellular transformation and are key targets for understanding virus-induced cancers.
Purpose of the Study:
- To identify and characterize a viral cyclin encoded by KSHV.
- To investigate the interaction and functional activity of the KSHV-encoded v-cyclin with cellular kinases.
Main Methods:
- DNA sequencing of a KSHV lambda clone from a Kaposi's sarcoma lesion.
- Expression and biochemical analysis of the KSHV v-cyclin protein.
- Co-immunoprecipitation assays to determine kinase interactions.
- In vitro kinase assays using GST-Rb fusion protein and histone H1 substrates.
Main Results:
- A KSHV open reading frame was identified with significant homology to HVS v-cyclin and human cyclin D2.
- The KSHV v-cyclin protein (29-30 kDa) associated predominantly with cdk6 and weakly with cdk4.
- KSHV v-cyclin-cdk6 complexes exhibited strong in vitro kinase activity, phosphorylating Rb and histone H1.
Conclusions:
- KSHV encodes a functional v-cyclin with properties similar to HVS v-cyclin.
- The KSHV v-cyclin specifically associates with and activates cdk6, suggesting a role in KSHV-mediated oncogenesis.