Document Detail


Survivin exists in immunochemically distinct subcellular pools and is involved in spindle microtubule function.
MedLine Citation:
PMID:  11861764     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Survivin is a member of the inhibitor of apoptosis gene family that has been implicated in both apoptosis inhibition and regulation of mitosis. However, the subcellular distribution of survivin has been controversial and variously described as a microtubule-associated protein or chromosomal passenger protein. Here, we show that antibodies directed to the survivin sequence Ala(3)-Ile(19) exclusively recognized a nuclear pool of survivin that segregated with nucleoplasmic proteins, but not with outer nuclear matrix or nuclear matrix proteins. By immunofluorescence, nuclear survivin localized to kinetochores of metaphase chromosomes, and to the central spindle midzone at anaphase. However, antibodies to Cys(57)-Trp(67) identified a cytosolic pool of survivin, which associated with interphase microtubules, centrosomes, spindle poles and mitotic spindle microtubules at metaphase and anaphase. Polyclonal antibodies recognizing survivin epitopes Ala(3)-Ile(19), Met(38)-Thr(48), Pro(47)-Phe(58) and Cys(57)-Trp(67) identified both survivin pools within the same mitotic cell. A ratio of approximately 1:6 for nuclear versus cytosolic survivin was obtained by quantitative subcellular fractionation. In synchronized cultures, cytosolic survivin abruptly increased at mitosis, physically associated with p34(cdc2), and was phosphorylated by p34(cdc2) on Thr(34), in vivo. By contrast, nuclear survivin began to accumulate in S phase, was not complexed with p34(cdc2) and was not phosphorylated on Thr(34). Intracellular loading of a polyclonal antibody to survivin caused microtubule defects and resulted in formation of multipolar mitotic spindles, but did not interfere with cytokinesis. These data demonstrate that although both reported localizations of survivin exist in mitotic cells, the preponderant survivin pool is associated with microtubules and participates in the assembly of a bipolar mitotic spindle.
Authors:
Paola Fortugno; Nathan R Wall; Alessandra Giodini; Daniel S O'Connor; Janet Plescia; Karen M Padgett; Simona Tognin; Pier Carlo Marchisio; Dario C Altieri
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of cell science     Volume:  115     ISSN:  0021-9533     ISO Abbreviation:  J. Cell. Sci.     Publication Date:  2002 Feb 
Date Detail:
Created Date:  2002-03-06     Completed Date:  2002-12-30     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0052457     Medline TA:  J Cell Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  575-85     Citation Subset:  IM    
Affiliation:
Boyer Center for Molecular Medicine, Department of Pathology, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal / metabolism
CDC2 Protein Kinase / metabolism
Cell Cycle / physiology
Cell Cycle Proteins / metabolism*
Cell Fractionation
Cell Nucleus / chemistry,  metabolism
Cysteine Proteinase Inhibitors / metabolism
Cytoplasm / chemistry,  metabolism
Cytoskeleton / metabolism
Hela Cells
Humans
Immunohistochemistry
Microtubule-Associated Proteins / immunology,  metabolism*
Microtubules / metabolism*
Mimosine / metabolism
Mitotic Spindle Apparatus / metabolism*
Neoplasm Proteins
Recombinant Proteins / metabolism
Grant Support
ID/Acronym/Agency:
CA78810/CA/NCI NIH HHS; CA90917/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/BIRC5 protein, human; 0/Cell Cycle Proteins; 0/Cysteine Proteinase Inhibitors; 0/Microtubule-Associated Proteins; 0/Neoplasm Proteins; 0/Recombinant Proteins; 500-44-7/Mimosine; EC 2.7.11.22/CDC2 Protein Kinase

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