title: The involvement of nuclear factor-κappaB in the nuclear targeting and cyclin E1 upregulating activities of hepatoma upregulated protein.
abstract: Hepatoma upregulated protein (HURP) is originally isolated during the search for the genes associated with hepatoma. HURP is upregulated in many human cancers. Culture cells exhibit transformed and invasive phenotype when ectopic HURP is introduced, revealing HURP as an oncogene candidate. Our previous studies demonstrated that Aurora-A regulated the cell transforming activities of HURP by phosphorylating HURP at four serines. To unravel how the Aurora-A/HURP cascade contributes to cell transformation, we firstly noticed that HURP shuttled between cytoplasm and nucleus. The nuclear localization activity of HURP was promoted or abolished by overexpression or knockdown of Aurora-A. Similarly, the HURP phosphorylation mimicking mutant 4E had higher nuclear targeting activity than the phosphorylation deficient mutant 4A. The HURP 4E accelerated G1 progression and upregulated cyclin E1, and the cyclin E1 upregulating and cell transforming activities of HURP were diminished when the nuclear localization signal (NLS) was removed from HURP. Furthermore, HURP employed p38/nuclear factor-κB (NF-κB) cascade to stimulate cell growth. Interestingly, NF-κB trapped HURP in nucleus by interacting with HURP 4E. At last, the HURP/NF-κB complex activated the cyclin E1 promoter. Collectively, Aurora-A/HURP relays cell transforming signal to NF-κB, and the HURP/NF-κB complex is engaged in the regulation of cyclin E1 expression.
authors.affiliation: Graduate Institute of Biomedicine and Biomedical Technology, National Chi Nan University, Taiwan.
authors.forename: Jo-Mei Maureen
authors.initials: JM
authors.lastname: Chen
authors.affiliation: Graduate Institute of Immunology, China Medical University, Taichung, Taiwan; Center for Neuropsychiatry, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Shao-Chih
authors.initials: SC
authors.lastname: Chiu
authors.affiliation: Department of Applied Chemistry, National Chi Nan University, Taiwan.
authors.forename: Tong-You Wade
authors.initials: TY
authors.lastname: Wei
authors.affiliation: Department of Applied Chemistry, National Chi Nan University, Taiwan.
authors.forename: Shin-Yi
authors.initials: SY
authors.lastname: Lin
authors.affiliation: Department of Applied Chemistry, National Chi Nan University, Taiwan.
authors.forename: Cheong-Meng
authors.initials: CM
authors.lastname: Chong
authors.affiliation: Graduate Institute of Biomedicine and Biomedical Technology, National Chi Nan University, Taiwan.
authors.forename: Chi-Chen
authors.initials: CC
authors.lastname: Wu
authors.affiliation: Graduate Institute of Biomedicine and Biomedical Technology, National Chi Nan University, Taiwan.
authors.forename: Jiao-Ying
authors.initials: JY
authors.lastname: Huang
authors.affiliation: Graduate Institute of Biomedicine and Biomedical Technology, National Chi Nan University, Taiwan.
authors.forename: Shu-Ting
authors.initials: ST
authors.lastname: Yang
authors.affiliation: Department of Applied Chemistry, National Chi Nan University, Taiwan.
authors.forename: Chia-Feng
authors.initials: CF
authors.lastname: Ku
authors.affiliation: Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Jiun-Yi
authors.initials: JY
authors.lastname: Hsia
authors.affiliation: Graduate Institute of Biomedicine and Biomedical Technology, National Chi Nan University, Taiwan; Department of Applied Chemistry, National Chi Nan University, Taiwan. Electronic address: ctyu@ncnu.edu.tw.
authors.forename: Chang-Tze Ricky
authors.initials: CT
authors.lastname: Yu
mesh_terms: D064096:Aurora Kinase A / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D019927:Cyclin E / Q000378:metabolism*; D016193:G1 Phase; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System; D016328:NF-kappa B / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D015513:Oncogene Proteins / Q000378:metabolism*; D010766:Phosphorylation; D021381:Protein Transport; D015854:Up-Regulation
chemical_list: C475820:CCNE1 protein, human; D019927:Cyclin E; C465041:DLGAP5 protein, human; D016328:NF-kappa B; D009363:Neoplasm Proteins; D015513:Oncogene Proteins; C576917:AURKA protein, human; D064096:Aurora Kinase A
keywords: Aurora-A; HURP; NF-κB; Nuclear targeting; Phosphorylation; p38