title: Cell cycle specific distribution of killin: evidence for negative regulation of both DNA and RNA synthesis.
abstract: p53 tumor-suppressor gene is a master transcription factor which controls cell cycle progression and apoptosis. killin was discovered as one of the p53 target genes implicated in S-phase control coupled to cell death. Due to its extreme proximity to pten tumor-suppressor gene on human chromosome 10, changes in epigenetic modification of killin have also been linked to Cowden syndrome as well as other human cancers. Previous studies revealed that Killin is a high-affinity DNA-binding protein with preference to single-stranded DNA, and it inhibits DNA synthesis in vitro and in vivo. Here, co-localization studies of RFP-Killin with either GFP-PCNA or endogenous single-stranded DNA binding protein RPA during S-phase show that Killin always adopts a mutually exclusive punctuated nuclear expression pattern with the 2 accessory proteins in DNA replication. In contrast, when cells are not in S-phase, RFP-Killin largely congregates in the nucleolus where rRNA transcription normally occurs. Both of these cell cycle specific localization patterns of RFP-Killin are stable under high salt condition, consistent with Killin being tightly associated with nucleic acids within cell nuclei. Together, these cell biological results provide a molecular basis for Killin in competitively inhibiting the formation of DNA replication forks during S-phase, as well as potentially negatively regulate RNA synthesis during other cell cycle phases.
authors.affiliation: a Center for Growth, Metabolism and Aging; Department of Biochemistry & Molecular Biology; School of Life Sciences; Sichuan University ; Chengdu , China.
authors.forename: Man
authors.initials: M
authors.lastname: Qiao
authors.forename: Dan
authors.initials: D
authors.lastname: Luo
authors.forename: Yi
authors.initials: Y
authors.lastname: Kuang
authors.forename: Haiyan
authors.initials: H
authors.lastname: Feng
authors.forename: Guangping
authors.initials: G
authors.lastname: Luo
authors.forename: Peng
authors.initials: P
authors.lastname: Liang
mesh_terms: D000818:Animals; D019556:COS Cells; D002453:Cell Cycle; D002466:Cell Nucleolus / Q000378:metabolism; D002522:Chlorocebus aethiops; D002875:Chromosomes / Q000235:genetics; D004247:DNA / Q000096:biosynthesis*; D004261:DNA Replication; D004277:DNA, Single-Stranded / Q000235:genetics; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D006801:Humans; D008164:Luminescent Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D010957:Plasmids / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis*; D016196:S Phase; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism*; D000097573:Red Fluorescent Protein
chemical_list: D004247:DNA; D004277:DNA, Single-Stranded; D008164:Luminescent Proteins; D018809:Proliferating Cell Nuclear Antigen; D012313:RNA; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D000097573:Red Fluorescent Protein; C554482:KLLN protein, human; C495901:TP53 protein, human
keywords: DNA replication forks; PCNA; RPA; killin; nucleolus; p53