Survivin exists in immunochemically distinct subcellular pools and is involved in spindle microtubule function - PubMed (original) (raw)
. 2002 Feb 1;115(Pt 3):575-85.
doi: 10.1242/jcs.115.3.575.
Affiliations
- PMID: 11861764
- DOI: 10.1242/jcs.115.3.575
Survivin exists in immunochemically distinct subcellular pools and is involved in spindle microtubule function
Paola Fortugno et al. J Cell Sci. 2002.
Abstract
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.
Similar articles
- Analysis of mitotic phosphorylation of borealin.
Kaur H, Stiff AC, Date DA, Taylor WR. Kaur H, et al. BMC Cell Biol. 2007 Jan 22;8:5. doi: 10.1186/1471-2121-8-5. BMC Cell Biol. 2007. PMID: 17241471 Free PMC article. - Survivin modulates microtubule dynamics and nucleation throughout the cell cycle.
Rosa J, Canovas P, Islam A, Altieri DC, Doxsey SJ. Rosa J, et al. Mol Biol Cell. 2006 Mar;17(3):1483-93. doi: 10.1091/mbc.e05-08-0723. Epub 2006 Jan 11. Mol Biol Cell. 2006. PMID: 16407408 Free PMC article. - Role of NuMA in vertebrate cells: review of an intriguing multifunctional protein.
Sun QY, Schatten H. Sun QY, et al. Front Biosci. 2006 Jan 1;11:1137-46. doi: 10.2741/1868. Front Biosci. 2006. PMID: 16146802 Review. - The roles of fission yeast ase1 in mitotic cell division, meiotic nuclear oscillation, and cytokinesis checkpoint signaling.
Yamashita A, Sato M, Fujita A, Yamamoto M, Toda T. Yamashita A, et al. Mol Biol Cell. 2005 Mar;16(3):1378-95. doi: 10.1091/mbc.e04-10-0859. Epub 2005 Jan 12. Mol Biol Cell. 2005. PMID: 15647375 Free PMC article. - [Role of survivin in mitosis].
Wolanin K, Piwocka K. Wolanin K, et al. Postepy Biochem. 2007;53(1):10-8. Postepy Biochem. 2007. PMID: 17718383 Review. Polish.
Cited by
- Pathogenetic model of survivin-dependent molecular signalling pathways in tumorigenesis of oral cancer and precursor lesions.
Aggarwal D, Shetty DC, Jain A, Gulati N, Juneja S. Aggarwal D, et al. J Oral Maxillofac Pathol. 2023 Apr-Jun;27(2):287-294. doi: 10.4103/jomfp.jomfp_5_23. Epub 2023 Jul 13. J Oral Maxillofac Pathol. 2023. PMID: 37854918 Free PMC article. - Prognostic value of XIAP and survivin expression in locally advanced breast cancer patients treated with anthracycline-based neoadjuvant chemotherapy.
Pluta P, Jesionek-Kupnicka D, Pluta A, Brzozowski K, Braun M, Kubicka-Wołkowska J, Piekarski J. Pluta P, et al. Arch Med Sci. 2019 Oct 7;19(2):343-354. doi: 10.5114/aoms.2019.88509. eCollection 2023. Arch Med Sci. 2019. PMID: 37034529 Free PMC article. - Survivin Small Molecules Inhibitors: Recent Advances and Challenges.
Albadari N, Li W. Albadari N, et al. Molecules. 2023 Feb 1;28(3):1376. doi: 10.3390/molecules28031376. Molecules. 2023. PMID: 36771042 Free PMC article. Review. - Mechanisms of Drug Resistance in Ovarian Cancer and Associated Gene Targets.
Alatise KL, Gardner S, Alexander-Bryant A. Alatise KL, et al. Cancers (Basel). 2022 Dec 18;14(24):6246. doi: 10.3390/cancers14246246. Cancers (Basel). 2022. PMID: 36551731 Free PMC article. Review. - Survivin Splice Variant 2β Enhances Pancreatic Ductal Adenocarcinoma Resistance to Gemcitabine.
Fuller RN, Kabagwira J, Vallejos PA, Folkerts AD, Wall NR. Fuller RN, et al. Onco Targets Ther. 2022 Oct 10;15:1147-1160. doi: 10.2147/OTT.S341720. eCollection 2022. Onco Targets Ther. 2022. PMID: 36238134 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous