The apoptotic v-cyclin–CDK6 complex phosphorylates and inactivates Bcl-2
Author: ["Päivi M. Ojala","Kazuhito Yamamoto","Esmeralda Castaños-Vélez","Peter Biberfeld","Stanley J. Korsmeyer","Tomi P. Mäkelä"]
Publication: Nature Cell Biology
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Abstract
v-cyclin encoded by Kaposi's sarcoma herpesvirus/human herpesvirus 8 (KSHV or HHV8) associates with cellular cyclin-dependent kinase 6 (CDK6) to form a kinase complex that promotes cell-cycle progression, but can also induce apoptosis in cells with high levels of CDK6. Here we show that whereas HHV8-encoded v-Bcl-2 protects against this apoptosis, cellular Bcl-2 has lost its anti-apoptotic potential as a result of an inactivating phosphorylation in its unstructured loop region. Moreover, we identify Bcl-2 as a new substrate for v-cyclin–CDK6 in vitro, and show that it is present in a complex with CDK6 in cell lysates. A Bcl-2 mutant with a S70A S87A double substitution in the loop region is not phosphorylated and provides resistance to apoptosis, indicating that inactivation of Bcl-2 by v-cyclin–CDK6 may be required for the observed apoptosis. Furthermore, the identification of phosphorylated Bcl-2 in HHV8-positive Kaposi's sarcoma indicates that HHV8-mediated interference with host apoptotic signalling pathways may encourage the development of Kaposi's sarcoma.
Cite this article
Ojala, P., Yamamoto, K., Castaños-Vélez, E. et al. The apoptotic v-cyclin–CDK6 complex phosphorylates and inactivates Bcl-2. Nat Cell Biol 2, 819–825 (2000). https://doi.org/10.1038/35041064
