title: Downregulation of POLD4 in Calu6 cells results in G1-S blockage through suppression of the Akt-Skp2-p27 pathway.
abstract: Previously, we have shown that downregulation of POLD4 in lung cancer cells delays progression through the G1-S cell cycle transition and leads to increased genomic instability. To date however, detailed molecular mechanisms have not been elucidated to explain how this occurs. In the present study, we found that reduction in POLD4 by siRNA knockdown promoted downregulation of both p-Akt Ser473 and Skp2 as well as upregulation of p27. Furthermore, these protein expression levels were rescued when siRNA-resistant POLD4 was ectopically expressed in the knockdown cells. These data suggest that the POLD4 downregulation is associated with impaired Akt-Skp2-p27 pathway in lung cancer.
authors.affiliation: Department of Pulmonary Medicine, Second Affiliated Hospital of Fujian Medical University, Fujian, China. Electronic address: hqm1003@hotmail.com.
authors.forename: Qinmiao
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Division of Molecular Carcinogenesis, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Motoshi
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Department of Pulmonary Medicine, Second Affiliated Hospital of Fujian Medical University, Fujian, China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Department of Pulmonary Medicine, Second Affiliated Hospital of Fujian Medical University, Fujian, China.
authors.forename: Huaping
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pulmonary Medicine, Second Affiliated Hospital of Fujian Medical University, Fujian, China.
authors.forename: Dongyong
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Pulmonary Medicine, Second Affiliated Hospital of Fujian Medical University, Fujian, China.
authors.forename: Huihuang
authors.initials: H
authors.lastname: Lin
mesh_terms: D045744:Cell Line, Tumor; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004258:DNA Polymerase III / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology*; D016196:S Phase / Q000187:drug effects; D044786:S-Phase Kinase-Associated Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D034741:RNA, Small Interfering; D044786:S-Phase Kinase-Associated Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051057:Proto-Oncogene Proteins c-akt; C521101:POLD4 protein, human; D004258:DNA Polymerase III
keywords: Checkpoint; DNA repair; DNA replication; Lung cancer; POLD4; Skp2