title: Cell Type- and Tissue Context-dependent Nuclear Distribution of Human Ago2.
abstract: Argonaute-2 protein (Ago2), a major component of RNA-induced silencing complex (RISC), has been viewed as a cytoplasmic protein. In this study, we demonstrated by immunofluorescence confocal microscopy that Ago2 is distributed mainly as a nuclear protein in primary human foreskin keratinocytes in monolayer cultures and their derived organotypic (raft) cultures, although it exhibits only a minimal level of nuclear distribution in continuous cell lines such as HeLa and HaCaT cells. Oncogenic human papillomavirus type 16 (HPV16) or type 18 (HPV18) infection of the keratinocytes does not affect the nuclear Ago2 distribution. Examination of human tissues reveals that Ago2 exhibits primarily as a nuclear protein in skin, normal cervix, and cervical cancer tissues, but not in larynx. Together, our data provide the first convincing evidence that the subcellular distribution of Ago2 occurs in a cell type- and tissue context-dependent manner and may correlate with its various functions in regulation of gene expression.
authors.affiliation: From the Tumor Virus RNA Biology Section, Gene Regulation and Chromosome Biology Laboratory, Center for Cancer Research, NCI, National Institutes of Health, Frederick, Maryland 21702.
authors.forename: Nishi R
authors.initials: NR
authors.lastname: Sharma
authors.affiliation: From the Tumor Virus RNA Biology Section, Gene Regulation and Chromosome Biology Laboratory, Center for Cancer Research, NCI, National Institutes of Health, Frederick, Maryland 21702.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wang
authors.affiliation: From the Tumor Virus RNA Biology Section, Gene Regulation and Chromosome Biology Laboratory, Center for Cancer Research, NCI, National Institutes of Health, Frederick, Maryland 21702.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Majerciak
authors.affiliation: From the Tumor Virus RNA Biology Section, Gene Regulation and Chromosome Biology Laboratory, Center for Cancer Research, NCI, National Institutes of Health, Frederick, Maryland 21702.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Ajiro
authors.affiliation: the Experimental Immunology Branch, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892, and.
authors.forename: Michael
authors.initials: M
authors.lastname: Kruhlak
authors.affiliation: the Department of Microbiology and Immunology, Penn State University School of Medicine, Hershey, Pennsylvania 17033.
authors.forename: Craig
authors.initials: C
authors.lastname: Meyers
authors.affiliation: From the Tumor Virus RNA Biology Section, Gene Regulation and Chromosome Biology Laboratory, Center for Cancer Research, NCI, National Institutes of Health, Frederick, Maryland 21702, zhengt@exchange.nih.gov.
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Zheng
mesh_terms: D060565:Argonaute Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D002584:Cervix Uteri / Q000378:metabolism / Q000821:virology; D005260:Female; D005786:Gene Expression Regulation; D020868:Gene Silencing; D057809:HEK293 Cells; D006367:HeLa Cells; D052162:Human papillomavirus 16; D052161:Human papillomavirus 18; D006801:Humans; D015603:Keratinocytes / Q000166:cytology; D007830:Larynx / Q000378:metabolism / Q000821:virology; D030361:Papillomavirus Infections / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000821:virology; D013347:Subcellular Fractions; D014018:Tissue Distribution; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000821:virology
chemical_list: C466422:AGO2 protein, human; D060565:Argonaute Proteins; D034741:RNA, Small Interfering
keywords: Ago2; RNA-binding protein; cervix; keratinocyte; keratinocytes; microRNA (miRNA); microscopic imaging; nuclear distribution; papillomavirus; virus