title: Role of dual specificity tyrosine-phosphorylation-regulated kinase 1B (Dyrk1B) in S-phase entry of HPV E7 expressing cells from quiescence.
abstract: The high-risk human papillomavirus (HPV) is the causative agent for cervical cancer. The HPV E7 oncogene promotes S-phase entry from quiescent state in the presence of elevated cell cycle inhibitor p27Kip1, a function that may contribute to carcinogenesis. However, the mechanism by which HPV E7 induces quiescent cells to entry into S-phase is not fully understood. Interestingly, we found that Dyrk1B, a dual-specificity kinase and negative regulator of cell proliferation in quiescent cells, was upregulated in E7 expressing cells. Surprisingly and in contrast to what was previously reported, Dyrk1B played a positive role in S-phase entry of quiescent HPV E7 expressing cells. Mechanistically, Dyrk1B contributed to p27 phosphorylation (at serine 10 and threonine 198), which was important for the proliferation of HPV E7 expressing cells. Moreover, Dyrk1B up-regulated HPV E7. Taken together, our studies uncovered a novel function of Dyrk1B in high-risk HPV E7-mediated cell proliferation. Dyrk1B may serve as a target for therapy in HPV-associated cancers.
authors: Cancer Research Center, Shandong University School of Medicine, Jinan, Shandong, China.
authors: Na
authors: N
authors: Zhou
authors: Cancer Research Center, Shandong University School of Medicine, Jinan, Shandong, China.
authors: Shoudao
authors: S
authors: Yuan
authors: Biology Institute of Shandong Academy of Sciences, Jinan, Shandong, China.
authors: Rongchun
authors: R
authors: Wang
authors: Institute of Pathogenic Biology, Shandong University School of Medicine, Jinan, Shandong, China.
authors: Weifang
authors: W
authors: Zhang
authors: Cancer Research Center, Shandong University School of Medicine, Jinan, Shandong, China.
authors: Jason J
authors: JJ
authors: Chen
mesh_terms: D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism; D050725:Papillomavirus E7 Proteins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D055213:Retinal Pigment Epithelium / Q000166:cytology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016196:S Phase / Q000502:physiology*; D000097603:Dyrk Kinases
chemical_list: D050725:Papillomavirus E7 Proteins; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D012333:RNA, Messenger; D000097603:Dyrk Kinases; C059731:oncogene protein E7, Human papillomavirus type 16
keywords: Dyrk1B; E7; HPV; S-phase; p27; quiescence