title: Ki-67 protein is associated with ribosomal RNA transcription in quiescent and proliferating cells.
abstract: The nuclear Ki-67 protein (pKi-67) has previously been shown to be exclusively expressed in proliferating cells. As a result, antibodies against this protein are widely used as prognostic tools in cancer diagnostics. Here we show, that despite the strong downregulation of pKi-67 expression in non-proliferating cells, the protein can nevertheless be detected at sites linked to ribosomal RNA (rRNA) synthesis. Although this finding does not argue against the use of pKi-67 as a proliferation marker, it has wide ranging implications for the elucidation of pKi-67 function. Employing the novel antibody TuBB-9, we could further demonstrate that also in proliferating cells, a fraction of pKi-67 is found at sites linked to the rRNA transcription machinery during interphase and mitosis. Moreover, chromatin immunoprecipitation (ChIP) assays provided evidence for a physical association of pKi-67 with chromatin of the promoter and transcribed region of the rRNA gene cluster. These data strongly suggest a role for pKi-67 in the early steps of rRNA synthesis.
authors.affiliation: Division of Tumour Biology, Research Center Borstel, Borstel, Germany.
authors.forename: Jörn
authors.initials: J
authors.lastname: Bullwinkel
authors.forename: Bettina
authors.initials: B
authors.lastname: Baron-Lühr
authors.forename: Anja
authors.initials: A
authors.lastname: Lüdemann
authors.forename: Claudia
authors.initials: C
authors.lastname: Wohlenberg
authors.forename: Johannes
authors.initials: J
authors.lastname: Gerdes
authors.forename: Thomas
authors.initials: T
authors.lastname: Scholzen
mesh_terms: D000974:Antibodies, Antinuclear / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000378:metabolism; D049109:Cell Proliferation; D016922:Cellular Senescence; D004256:DNA Polymerase I / Q000378:metabolism; D004275:DNA, Ribosomal; D000939:Epitopes; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D007399:Interphase; D019394:Ki-67 Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008221:Lymphoid Tissue / Q000378:metabolism; D008938:Mitosis; D009000:Monocytes / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012335:RNA, Ribosomal / Q000096:biosynthesis*; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D004275:DNA, Ribosomal; D000939:Epitopes; D019394:Ki-67 Antigen; C440408:MIB-1 antibody; D012335:RNA, Ribosomal; D004256:DNA Polymerase I