biostudies-literatureSteingruber MProF1 FranceDeutsche Forschungsgemeinschaft6188-6203https://www.ebi.ac.uk/biostudies/studies/S-EPMC6463711biostudies-literatureUnknown294(15)Human cytomegalovirus (HCMV) is a common β-herpesvirus causing life-long latent infections. HCMV replication interferes with cell cycle regulation in host cells because the HCMV-encoded cyclin-dependent kinase (CDK) ortholog pUL97 extensively phosphorylates the checkpoint regulator retinoblastoma protein. pUL97 also interacts with cyclins B1, T1, and H, and recent findings have strongly suggested that these interactions influence pUL97 substrate recognition. Interestingly, here we detected profound mechanistic differences among these pUL97-cyclin interactions. Our study revealed the following. (i) pUL97 interacts with cyclins B1 and H in a manner dependent on pUL97 activity and HCMV-specific cyclin modulation, respectively. (ii) The phosphorylated state of both proteins is an important detThe Journal of biological chemistryCyclins B1, T1, and H differ in their molecular mode of interaction with cytomegalovirus protein kinase pUL97.PMC6463711PL236/7–1ANR-10-INBS-08–01MA1289/8–1STI155/5–1Ferre SCoute YHahn FBuscher NKeller LSticht HMarschall MSteingruber MSocher EHesse AMPlachter BfalseCyclins B1, T1, and H differ in their molecular mode of interaction with cytomegalovirus protein kinase pUL97.Human cytomegalovirus (HCMV) is a common β-herpesvirus causing life-long latent infections. HCMV replication interferes with cell cycle regulation in host cells because the HCMV-encoded cyclin-dependent kinase (CDK) ortholog pUL97 extensively phosphorylates the checkpoint regulator retinoblastoma protein. pUL97 also interacts with cyclins B1, T1, and H, and recent findings have strongly suggested that these interactions influence pUL97 substrate recognition. Interestingly, here we detected profound mechanistic differences among these pUL97-cyclin interactions. Our study revealed the following. (i) pUL97 interacts with cyclins B1 and H in a manner dependent on pUL97 activity and HCMV-specific cyclin modulation, respectively. (ii) The phosphorylated state of both proteins is an important det2019-01-01T00:00:00Z2019 Apr2026-04-29T22:54:42.523Z2025-04-04T09:44:09.102ZS-EPMC64637113078284010.1074/jbc.RA118.00704910.1074/jbc.ra118.007049