Document Detail


The location of pKi67 in the outer dense fibrillary compartment of the nucleolus points to a role in ribosome biogenesis during the cell division cycle.
MedLine Citation:
PMID:  10727979     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Although widely used as a marker of cell proliferation, the biochemical properties and function of the Ki67 antigen remain poorly understood. Recent data indicate that it can interact with RNA, DNA, and a number of cellular proteins including elements of the ubiquitin proteolytic pathway and a novel kinase. The evidence for its expression only in cycling cells is extensive and it is not regulated by stress, apoptosis or DNA damage. It was reasoned that a detailed characterization of the localization of pKi67 and analysis of its spatial relationship to other nucleolar proteins may provide insights into its function. Using high-resolution laser scanning confocal microscopy with double and triple labelling, pKi67 expression in MCF7 cells has been defined in relation to the distribution of nucleolin, fibrillarin, p130 (human Nopp 140 homologue), p120 (Nol 1), RH-II/Gu helicase, and topoisomerase II beta. All of these molecules are perichromosomal during mitosis and all but fibrillarin and p130 show extra-nucleolar distribution in early G1. The majority of p120 (Nol 1) and RH-II/Gu helicase co-localize in the diffuse fibrillar centre (DFC) of nucleoli, while there is only partial overlap with nucleolin and fibrillarin. There is no co-localization between p130 and pKi67. These data refine current understanding of the distribution of pKi67 and its physical relationship with functional domains of the nucleolus and place pKi67 in a zone of the DFC associated with late rRNA processing. Taken together with recent biochemical data, these observations allow the proposal of a model of pKi67 function in which it acts as an 'efficiency factor' in ribosome biogenesis during the heavy metabolic demands placed on a cell during the cell division cycle.
Authors:
D E MacCallum; P A Hall
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of pathology     Volume:  190     ISSN:  0022-3417     ISO Abbreviation:  J. Pathol.     Publication Date:  2000 Apr 
Date Detail:
Created Date:  2000-06-08     Completed Date:  2000-06-08     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0204634     Medline TA:  J Pathol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  537-44     Citation Subset:  IM    
Copyright Information:
Copyright 2000 John Wiley & Sons, Ltd.
Affiliation:
Department of Molecular and Cellular Pathology, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK.
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MeSH Terms
Descriptor/Qualifier:
Blood Proteins / metabolism
Carrier Proteins / metabolism
Cell Division / physiology
Cell Nucleolus / metabolism*
Chromosomal Proteins, Non-Histone / metabolism
DNA Topoisomerases, Type II / metabolism
DNA-Binding Proteins
Female
Humans
Ki-67 Antigen / metabolism*,  physiology
Microscopy, Confocal
Nuclear Proteins / metabolism
Phosphoproteins / metabolism
Protein Inhibitors of Activated STAT
Proteins*
RNA Helicases / metabolism
RNA-Binding Proteins / metabolism
Retinoblastoma-Like Protein p130
Ribosomes / metabolism
Small Ubiquitin-Related Modifier Proteins*
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Blood Proteins; 0/Carrier Proteins; 0/Chromosomal Proteins, Non-Histone; 0/DNA-Binding Proteins; 0/Ki-67 Antigen; 0/NOL1 protein, human; 0/Nuclear Proteins; 0/PIAS1 protein, human; 0/Phosphoproteins; 0/Protein Inhibitors of Activated STAT; 0/Proteins; 0/RNA-Binding Proteins; 0/Retinoblastoma-Like Protein p130; 0/Small Ubiquitin-Related Modifier Proteins; 0/fibrillarin; 0/nucleolin; EC 2.7.7.-/RNA Helicases; EC 5.99.1.3/DNA Topoisomerases, Type II; EC 5.99.1.3/DNA topoisomerase II beta

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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