Document Detail


PAR, a protein involved in the cell cycle, is functionally related to chromosomal passenger proteins.
MedLine Citation:
PMID:  21225229     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Prostate androgen regulated (PAR) protein is a 148 amino acid polypeptide ubiquitously expressed in normal cells and overexpressed in many malignancies. Manipulation of PAR mRNA in DU145 and NIH3T3 cells indicated that its expression level is an important determinant of cell in vitro proliferation, clonogenicity in soft agar and in vivo tumorigenicity. In this study, we showed that PAR is a short-lived protein with a peak in G2/M phase. Using immunofluorescent antibodies we showed that PAR moves from centrosomes in prophase and metaphase to spindle midzone in anaphase, and concentrates to midbody in telophase and cytokinesis. During mitosis a fraction of PAR can also be detected in the cytoplasm. PAR pattern of expression and its dynamic localization suggested a functional relationship to chromosomal passenger proteins (CPP). This protein colocalized with Aurora A at centrosomes in metaphase, and with survivin at midbody in telophase and cytokinesis. It also formed complexes with Aurora A, and with survivin, Aurora B and INCENP. In addition, PAR increased Aurora B kinase activity on histone H3. The decreased PAR levels in DU145 cells resulted in defects in centrosome segregation, in failed cytokinesis and chromosome alignment, and in increased number of apoptotic cells, polyploidy and aberrant mitosis. It is known that such defects could lead to genomic instability and tumorigenesis. In this study we also confirm our earlier findings that PAR is overexpressed in many tumors. Due to its involvement in cell cycle and its overexpression in several human cancers PAR could represent an attractive target for therapeutic intervention.
Authors:
Micsunica Platica; Alin Ionescu; Elena Ivan; James F Holland; John Mandeli; Ovidiu Platica
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-01-11
Journal Detail:
Title:  International journal of oncology     Volume:  38     ISSN:  1791-2423     ISO Abbreviation:  Int. J. Oncol.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-02-03     Completed Date:  2011-06-06     Revised Date:  2011-07-11    
Medline Journal Info:
Nlm Unique ID:  9306042     Medline TA:  Int J Oncol     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  777-85     Citation Subset:  IM    
Affiliation:
Department of Medicine, The Tisch Cancer Institute, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Cycle Proteins / chemistry,  genetics,  metabolism,  physiology
Cell Line, Tumor
Chromosomal Proteins, Non-Histone / chemistry,  genetics,  metabolism,  physiology*
Female
Gene Expression Regulation, Neoplastic
Humans
Male
Membrane Proteins / chemistry,  genetics,  metabolism,  physiology*
Mice
Mitosis / genetics
NIH 3T3 Cells
Neoplasm Proteins / chemistry,  genetics,  metabolism,  physiology*
Neoplasms / genetics,  metabolism
Protein-Serine-Threonine Kinases / metabolism
Sequence Homology, Amino Acid
Tissue Distribution
Up-Regulation
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins; 0/Chromosomal Proteins, Non-Histone; 0/INCENP protein, human; 0/JTB protein, human; 0/Membrane Proteins; 0/Neoplasm Proteins; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/aurora kinase

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


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