The regulatory role of protein phosphorylation in human gammaherpesvirus associated cancers

Abstract

Activation of specific sets of protein kinases by intracellular signal molecules has become more and more apparent in the past decade. Phosphorylation, one of key posttranslational modification events, is activated by kinase or regulatory protein and is vital for controlling many physiological functions of eukaryotic cells such as cell proliferation, differentiation, malignant transformation, and signal transduction mediated by external stimuli. Moreovers, the reversible modification of phosphorylation and dephosphorylation can result in different features of the target substrate molecules including DNA binding, protein-protein interaction, subcellular location and enzymatic activity, and is often hijacked by viral infection. Epstein-Barr virus (EBV) and Kaposi's sarcomaassociated herpesvirus (KSHV), two human oncogenic gamma-herpesviruses, are shown to tightly associate with many malignancies. In this review, we summarize the recent progresses on understanding of molecular properties and regulatory modes of cellular and viral proteins phosphorylation influenced by these two tumor viruses, and highlight the potential therapeutic targets and strategies against their related cancers.

The mechanism of BUD13 m6A methylation mediated MBNL1-phosphorylation by CDK12 regulating the vasculogenic mimicry in glioblastoma cells

“…The IPTMnet database and iGPS database predicted that CDK12 phosphorylating MBNL1 at T6 site. Phosphorylation, as one of the most common protein modifications, regulates cell proliferation, differentiation, and signal transduction [ 56 ], and plays an important regulatory role in glioma. SMURF2 Thr249 phosphorylation regulated GBM aggressiveness through TGFBR-SMAD-SOX4 axis [ 57 ].…”

Molecular Determinants and the Regulation of Human Cytomegalovirus Latency and Reactivation

“…Herpesvirus latency is associated with profound changes in cell signaling to modulate survival, sensing, and differentiation [ 53 , 113 , 114 ]. In the case of HCMV infection in monocytes, these changes include increasing MCP-1 to enhance cellular migration, promotion of immune response genes, increase protein and lipid metabolism, and a dramatic shift in the differentiation profile toward macrophages [ 115 , 116 , 117 ].…”

Exploring the Drug Potential of Phytochemicals as a Novel Therapeutic Drug Candidate for Herpesvirus: An In-silico Evaluation

“…Especially, the herpesvirus viruses such as Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus are known as human herpesvirus-4 and human herpesvirus-8, which are considered to be the main causative agents of lymphomagenesis in immunocompromised people. Specifically, these viruses are responsible for causing numerous lymphoproliferative and neoplastic diseases in the human race [5]. These viruses have also been reported to be involved in a number of cellular signaling pathways involved in phosphorylation and dephosphorylation functions [5].…”

“…Specifically, these viruses are responsible for causing numerous lymphoproliferative and neoplastic diseases in the human race [5]. These viruses have also been reported to be involved in a number of cellular signaling pathways involved in phosphorylation and dephosphorylation functions [5].…”