Protein kinases responsible for the phosphorylation of the nuclear egress core complex of human cytomegalovirus

• DOI: 10.1099/jgv.0.000931
• Publication Date: 2017-09-26T12:12:29Z
• Authors: Eric Sonntag; Jens Milbradt; Adriana Svrlanska; Hanife Strojan; Sigrun Häge; Alexandra Kraut; Anne-Marie Hesse; Bushra Amin; Uwe Sonnewald; Yohann Couté; Manfred Marschall
• Keywords: Phosphorylation cascade

Nuclear egress of herpesvirus capsids is mediated by a multi-component nuclear complex (NEC) assembled heterodimer two essential viral core proteins. In the case human cytomegalovirus (HCMV), this NEC defined interaction between membrane-anchored pUL50 and its cofactor, pUL53. protein phosphorylation considered to be an important regulatory step, so study focused on respective role cellular kinases. Multiply phosphorylated varieties were detected Western blot Phos-tag analyses as resulting from both kinase activities. vitro demonstrated that substrate PKCα CDK1, while pUL53 can also moderately CDK1. The use inhibitors further illustrated importance distinct kinases for phosphorylation. Importantly, mass spectrometry-based proteomic identified five major nine minor sites functional relevance was confirmed various experimental settings, including knock-down/knock-out confocal imaging, in which it found (i) HCMV proteins are not solely pUL97, but kinases; (ii) PKC CDK1 detectable pUL50; (iii) no impact functionality has been far; (iv) nonetheless, CDK1-specific appears required interaction. summary, our findings provide first evidence kinases, pattern relevance.