|
|
|
|
|
|
|
|
|||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
Research Article |
1 Boyer Center for Molecular Medicine, Department of Pathology, Yale University
School of Medicine, 295 Congress Avenue, New Haven, CT 06536, USA
2 NOVUS Biologicals, Inc. P.O. Box 802, Littleton, CO 80160, USA
3 Vita-Salute University School of Medicine, San Raffaele Scientific Institute,
Via Olgettina 58, Milano, 20132, Italy
Author for correspondence (e-mail: dario.altieri{at}yale.edu)
Accepted 23 October 2001
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 Ala3-Ile19 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
Cys57-Trp67 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 Ala3-Ile19,
Met38-Thr48, Pro47-Phe58 and
Cys57-Trp67 identified both survivin pools within the
same mitotic cell. A ratio of 
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 p34cdc2, and was phosphorylated by
p34cdc2 on Thr34, in vivo. By contrast, nuclear survivin
began to accumulate in S phase, was not complexed with p34cdc2 and
was not phosphorylated on Thr34. 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.
Key words: Survivin, Microtubules, Mitotic spindle, Kinetochore, p34cdc2
This article has been cited by other articles:
|
|
 |
|
  Y. Jiang, W. Nishimura, D. Devor-Henneman, D. Kusewitt, H. Wang, M. P. Holloway, T. Dohi, E. Sabo, M. L. Robinson, D. C. Altieri, et al. Postnatal Expansion of the Pancreatic {beta}-Cell Mass Is Dependent on Survivin Diabetes, October 1, 2008; 57(10): 2718 - 2727. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Brennan, E. Rexhepaj, S. L. O'Brien, E. McSherry, D. P. O'Connor, A. Fagan, A. C. Culhane, D. G. Higgins, K. Jirstrom, R. C. Millikan, et al. Altered Cytoplasmic-to-Nuclear Ratio of Survivin Is a Prognostic Indicator in Breast Cancer Clin. Cancer Res., May 1, 2008; 14(9): 2681 - 2689. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Hu, Y. Shikama, I. Matsuoka, and J. Kimura Terminally differentiated neutrophils predominantly express Survivin-2{alpha}, a dominant-negative isoform of Survivin J. Leukoc. Biol., February 1, 2008; 83(2): 393 - 400. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Troeger, M. Siepermann, G. Escherich, R. Meisel, R. Willers, S. Gudowius, T. Moritz, H.-J. Laws, H. Hanenberg, U. Goebel, et al. Survivin and its prognostic significance in pediatric acute B-cell precursor lymphoblastic leukemia Haematologica, August 1, 2007; 92(8): 1043 - 1050. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Pina-Oviedo, K. Urbanska, S. Radhakrishnan, T. Sweet, K. Reiss, K. Khalili, and L. Del Valle Effects of JC Virus Infection on Anti-Apoptotic Protein Survivin in Progressive Multifocal Leukoencephalopathy Am. J. Pathol., April 1, 2007; 170(4): 1291 - 1304. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Caldas, J. R. Fangusaro, D. R. Boue, M. P. Holloway, and R. A. Altura Dissecting the role of endothelial SURVIVIN {Delta}Ex3 in angiogenesis Blood, February 15, 2007; 109(4): 1479 - 1489. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Marconi, K. Dallaglio, R. Lotti, C. Vaschieri, F. Truzzi, F. Fantini, and C. Pincelli Survivin Identifies Keratinocyte Stem Cells and Is Downregulated by Anti-{beta}1 Integrin During Anoikis Stem Cells, January 1, 2007; 25(1): 149 - 155. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Cosgrave, A. D K Hill, and L. S Young Growth factor-dependent regulation of survivin by c-myc in human breast cancer J. Mol. Endocrinol., December 1, 2006; 37(3): 377 - 390. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ceruti, A. Mazzola, and M. P. Abbracchio Proteasome Inhibitors Potentiate Etoposide-Induced Cell Death in Human Astrocytoma Cells Bearing a Mutated p53 Isoform J. Pharmacol. Exp. Ther., December 1, 2006; 319(3): 1424 - 1434. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. H. Kang and D. C. Altieri Regulation of Survivin Stability by the Aryl Hydrocarbon Receptor-interacting Protein J. Biol. Chem., August 25, 2006; 281(34): 24721 - 24727. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. M. Ryan, G. E. Konecny, S. Kahlert, H.-J. Wang, M. Untch, G. Meng, M. D. Pegram, K. C. Podratz, J. Crown, D. J. Slamon, et al. Survivin expression in breast cancer predicts clinical outcome and is associated with HER2, VEGF, urokinase plasminogen activator and PAI-1 Ann. Onc., April 1, 2006; 17(4): 597 - 604. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Rosa, P. Canovas, A. Islam, D. C. Altieri, and S. J. Doxsey Survivin Modulates Microtubule Dynamics and Nucleation throughout the Cell Cycle Mol. Biol. Cell, March 1, 2006; 17(3): 1483 - 1493. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Xia, J. Bisi, J. Strum, L. Liu, K. Carrick, K. M. Graham, A. L. Treece, M. A. Hardwicke, M. Dush, Q. Liao, et al. Regulation of Survivin by ErbB2 Signaling: Therapeutic Implications for ErbB2-Overexpressing Breast Cancers Cancer Res., February 1, 2006; 66(3): 1640 - 1647. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wu, X. Ling, D. Pan, P. Apontes, L. Song, P. Liang, D. C. Altieri, T. Beerman, and F. Li Molecular Mechanism of Inhibition of Survivin Transcription by the GC-rich Sequence-selective DNA Binding Antitumor Agent, Hedamycin: EVIDENCE OF SURVIVIN DOWN-REGULATION ASSOCIATED WITH DRUG SENSITIVITY J. Biol. Chem., March 11, 2005; 280(10): 9745 - 9751. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Samuel, K. Okada, M. Hyer, K. Welsh, J. M. Zapata, and J. C. Reed cIAP1 Localizes to the Nuclear Compartment and Modulates the Cell Cycle Cancer Res., January 1, 2005; 65(1): 210 - 218. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Johnson and E. W. Howerth Survivin: A Bifunctional Inhibitor of Apoptosis Protein Vet. Pathol., November 1, 2004; 41(6): 599 - 607. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Vischioni, P. van der Valk, S. W. Span, F. A. E. Kruyt, J. A. Rodriguez, and G. Giaccone Nuclear localization of survivin is a positive prognostic factor for survival in advanced non-small-cell lung cancer Ann. Onc., November 1, 2004; 15(11): 1654 - 1660. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Yang, A. Welm, and J. M. Bishop Cell division and cell survival in the absence of survivin PNAS, October 19, 2004; 101(42): 15100 - 15105. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. A. Beardmore, L. J. Ahonen, G. J. Gorbsky, and M. J. Kallio Survivin dynamics increases at centromeres during G2/M phase transition and is regulated by microtubule-attachment and Aurora B kinase activity J. Cell Sci., August 15, 2004; 117(18): 4033 - 4042. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Dohi, K. Okada, F. Xia, C. E. Wilford, T. Samuel, K. Welsh, H. Marusawa, H. Zou, R. Armstrong, S.-i. Matsuzawa, et al. An IAP-IAP Complex Inhibits Apoptosis J. Biol. Chem., August 13, 2004; 279(33): 34087 - 34090. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Iurlaro, F. Demontis, M. Corada, L. Zanetta, C. Drake, M. Gariboldi, S. Peiro, A. Cano, P. Navarro, A. Cattelino, et al. VE-Cadherin Expression and Clustering Maintain Low Levels of Survivin in Endothelial Cells Am. J. Pathol., July 1, 2004; 165(1): 181 - 189. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. J. Schlette, L. J. Medeiros, A. Goy, R. Lai, and G. Z. Rassidakis Survivin Expression Predicts Poorer Prognosis in Anaplastic Large-Cell Lymphoma J. Clin. Oncol., May 1, 2004; 22(9): 1682 - 1688. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Martinez, B. Bellosillo, F. Bosch, A. Ferrer, S. Marce, N. Villamor, G. Ott, E. Montserrat, E. Campo, and D. Colomer Nuclear Survivin Expression in Mantle Cell Lymphoma Is Associated with Cell Proliferation and Survival Am. J. Pathol., February 1, 2004; 164(2): 501 - 510. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Beltrami, J. Plescia, J. C. Wilkinson, C. S. Duckett, and D. C. Altieri Acute Ablation of Survivin Uncovers p53-dependent Mitotic Checkpoint Functions and Control of Mitochondrial Apoptosis J. Biol. Chem., January 16, 2004; 279(3): 2077 - 2084. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Fukuda, C. R. Mantel, and L. M. Pelus Survivin regulates hematopoietic progenitor cell proliferation through p21WAF1/Cip1-dependent and -independent pathways Blood, January 1, 2004; 103(1): 120 - 127. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Fornaro, J. Plescia, S. Chheang, G. Tallini, Y.-M. Zhu, M. King, D. C. Altieri, and L. R. Languino Fibronectin Protects Prostate Cancer Cells from Tumor Necrosis Factor-{alpha}-induced Apoptosis via the AKT/Survivin Pathway J. Biol. Chem., December 12, 2003; 278(50): 50402 - 50411. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Fortugno, E. Beltrami, J. Plescia, J. Fontana, D. Pradhan, P. C. Marchisio, W. C. Sessa, and D. C. Altieri Regulation of survivin function by Hsp90 PNAS, November 25, 2003; 100(24): 13791 - 13796. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Lo Muzio, G. Pannone, R. Leonardi, S. Staibano, M.D. Mignogna, G. De Rosa, Y. Kudo, T. Takata, and D.C. Altieri Survivin, a Potential Early Predictor of Tumor Progression in the Oral Mucosa J. Dent. Res., November 1, 2003; 82(11): 923 - 928. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Carvalho, M. Carmena, C. Sambade, W. C. Earnshaw, and S. P. Wheatley Survivin is required for stable checkpoint activation in taxol-treated HeLa cells J. Cell Sci., July 15, 2003; 116(14): 2987 - 2998. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Schmidt, K. Schag, M. R. Muller, M. M. Weck, S. Appel, L. Kanz, F. Grunebach, and P. Brossart Survivin is a shared tumor-associated antigen expressed in a broad variety of malignancies and recognized by specific cytotoxic T cells Blood, July 15, 2003; 102(2): 571 - 576. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. P. Blanc-Brude, M. Mesri, N. R. Wall, J. Plescia, T. Dohi, and D. C. Altieri Therapeutic Targeting of the Survivin Pathway in Cancer: Initiation of Mitochondrial Apoptosis and Suppression of Tumor-associated Angiogenesis Clin. Cancer Res., July 1, 2003; 9(7): 2683 - 2692. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Song, X. Yao, and M. Wu Direct Interaction between Survivin and Smac/DIABLO Is Essential for the Anti-apoptotic Activity of Survivin during Taxol-induced Apoptosis J. Biol. Chem., June 13, 2003; 278(25): 23130 - 23140. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kappler, M. Kotzsch, F. Bartel, S. Fussel, C. Lautenschlager, U. Schmidt, P. Wurl, M. Bache, H. Schmidt, H. Taubert, et al. Elevated Expression Level of Survivin Protein in Soft-Tissue Sarcomas Is a Strong Independent Predictor of Survival Clin. Cancer Res., March 1, 2003; 9(3): 1098 - 1104. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Allen, S. R. Florell, A. N. Hanks, A. Alexander, M. J. Diedrich, D. C. Altieri, and D. Grossman Survivin Expression in Mouse Skin Prevents Papilloma Regression and Promotes Chemical-induced Tumor Progression Cancer Res., February 1, 2003; 63(3): 567 - 572. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Temme, M. Rieger, F. Reber, D. Lindemann, B. Weigle, P. Diestelkoetter-Bachert, G. Ehninger, M. Tatsuka, Y. Terada, and E. P. Rieber Localization, Dynamics, and Function of Survivin Revealed by Expression of Functional SurvivinDsRed Fusion Proteins in the Living Cell Mol. Biol. Cell, January 1, 2003; 14(1): 78 - 92. [Abstract] [Full Text]
|
|
|
|
|
|
A. Giodini, M. J. Kallio, N. R. Wall, G. J. Gorbsky, S. Tognin, P. C. Marchisio, M. Symons, and D. C. Altieri Regulation of Microtubule Stability and Mitotic Progression by Survivin Cancer Res., May 1, 2002; 62(9): 2462 - 2467. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Tran, Z. Master, J. L. Yu, J. Rak, D. J. Dumont, and R. S. Kerbel A role for survivin in chemoresistance of endothelial cells mediated by VEGF PNAS, April 2, 2002; 99(7): 4349 - 4354. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Tran, Z. Master, J. L. Yu, J. Rak, D. J. Dumont, and R. S. Kerbel A role for survivin in chemoresistance of endothelial cells mediated by VEGF PNAS, April 2, 2002; 99(7): 4349 - 4354. [Abstract] [Full Text] [PDF]
|
|
