Champeris Tsaniras, Spyridon

Taraviras, Stavros

Vlachakis, Dimitrios

English

Journal of Molecular Biochemistry

Editorial Spyridon Champeris Tsaniras1, Dimitrios Vlachakis2 and Stavros Taraviras1 1 Department of Physiology, Medical School, University of Patras, Rio, 26504 Patras, Greece 2 Computational Biology & Medicine Group, Biomedical Research Foundation, Academy of Athens, Soranou Efessiou 4, Athens 11527, Greece Correspondence should be addressed to Stavros Taraviras; Tel: +30 2610997943, Fax: +30 2610997215, E-mail: taraviras@med.upatras.gr The Nucleophosmin-Pin1 interaction links the cell cycle, cancer and pluripotency In the current issue of J Mol Biochem, Zhao et al. (2015) characterize the phosphorylation sites of nu-cleophosmin (Npm); a protein involved, among others, in licensing of centrosome duplication during the cell cycle. The authors also identify a functional interaction of Npm with the Pin1 isomerase, taking place during mitosis. They show that mutating one of the possible Npm binding sites results in cell division defects and a decrease in mitotic cell number. The latter is of special significance, suggesting that Npm post -phosphorylation plays a role in cell cycle progression. But perhaps the most interesting aspect in this story is the emerging link between the cell cycle, cancer and pluripotency.  Excessive centrosome numbers have been re-ported to disrupt proper chromosome segregation, which, in turn, is correlated to oncogenesis (Godinho & Pellman 2014). In line with this, high Pin1 expres-sion has been reported in a plethora of human cancers (Bao et al. 2004), and has been associated with poor prognosis (reviewed by Lu & Hunter 2014). Its over-expression has been reported to induce chromosomal instability, in vitro cell transformation as well as malignant mammary tumors in transgenic mice (Suizu et al. 2006). In addition, Npm is overex-pressed in a large number of human cancers (reviewed by Grisendi et al. 2006) and has been proposed to have oncogenic properties (Lim & Wang 2006) but its ablation has also been linked to centro-some overduplication and genomic instability (Grisendi et al. 2005).  Interestingly, both NPM and Pin1 are linked to pluripotency. The former was first identified in a ge-nome-wide screen for pluripotency regulators; further analysis suggested that it promotes the self-renewal of embryonic stem (ES) cells via the RNA-binding pro-tein Mki67ip (Abujarour et al. 2010). In line with this, Johansson and Simonsson (2010) found that, in ES cells, each of the core ES cell transcription factors Oct4, Sox2 and Nanog independently formed com-plexes with Npm1. They further showed that these in-teractions were affected by the routes of differentiation and that Npm1 downregulation increased the expres-sion of mesodermal and ectodermal genes, while they identified that Npm also interacts with Translationally controlled tumor protein (Tpt1) during ES cell mitosis (Johansson et al. 2010). Similarly, Pin1 was found to interact and stabilise Nanog, a critical mechanism for their ability to self-renew and form teratomas in mice (Moretto-Zita et al. 2010). Nishi et al. (2011) showed that Pin1 also regulates phosphorylated Oct4 and is essential for the maintenance of the pluripotent state.  All the above can be seen within a new con-text, with the novel identification of Npm-Pin1 interac-tion, reported in this issue. The interplay between the cell cycle, pluripotency and cancer  has only recently gained attention and seems to be extremely compli-cated and multidirectional (Champeris Tsaniras et al. 2014); however, a better understanding is on the way, as more and more links begin to unravel.  References  Abujarour R, Efe J & Ding S 2010 Genome-wide gain-of-function screen identifies novel regulators of pluri-potency. Stem Cells 28 1487-1497 Bao L, Kimzey A, Sauter G, Sowadski JM, Lu KP & Wang DG 2004 Prevalent overexpression of prolyl isomerase Pin1 in human cancers. Am J Pathol 164 1727-1737 Champeris Tsaniras S, Kanellakis N, Symeonidou IE, Nikolopoulou P, Lygerou Z & Taraviras S 2014 Li-censing of DNA replication, cancer, pluripotency and differentiation: an interlinked world? Semin Cell Dev Biol 30 174-180 Godinho SA & Pellman D 2014 Causes and conse-quences of centrosome abnormalities in cancer. Philos Trans R Soc Lond B Biol Sci 369 pii: 20130467 Journal of Molecular Biochemistry (2015) 4, 50-51 © The Author(s) 2015. Published by Lorem Ipsum Press. Grisendi S, Bernardi R, Rossi M, Cheng K, Khandker L, Manova K & Pandolfi PP 2005 Role of nucleophos-min in embryonic development and tumorigenesis. Nature 437 147-153 Grisendi S, Mecucci C, Falini B & Pandolfi PP 2006 Nucleophosmin and cancer. Nat Rev Cancer 6 493-505 Johansson H & Simonsson S 2010 Core transcription factors, Oct4, Sox2 and Nanog, individually form complexes with nucleophosmin (Npm1) to control em-bryonic stem (ES) cell fate determination. Aging 2 815-822 Johansson H, Vizlin-Hodzic D, Simonsson T & Si-monsson S 2010 Translationally controlled tumor pro-tein interacts with nucleophosmin during mitosis in ES cells. Cell Cycle 9 2160-2169 Lim MJ & Wang XW 2006 Nucleophosmin and hu-man cancer. Cancer Detect Prev 30 481-490 Lu Z & Hunter T 2014 Prolyl isomerase Pin1 in can-cer. Cell Res 24 1033-1049 Moretto-Zita M, Jin H, Shen Z, Zhao T, Briggs SP & Xu Y 2010 Phosphorylation stabilizes Nanog by pro-moting its interaction with Pin1. Proc Natl Acad Sci U S A 107 13312-13317 Nishi M, Akutsu H, Masui S, Kondo A, Nagashima Y, Kimura H, Perrem K, Shigeri Y, Toyoda M, Okayama A, Hirano H, Umezawa A, Yamamoto N, Lee SW & Ryo A 2011 A distinct role for Pin1 in the induction and maintenance of pluripotency. J Biol Chem 286 11593-11603 Zhao X, Ji J, Yu L-R, Veenstra T, Lu KP & Wang XW 2015 Cell cycle-dependent phosphorylation of nucleo-phosmin and its potential regulation by peptidyl-prolyl cis/trans isomerase.  J Mol Biochem 4 95-103 51  Journal of Molecular Biochemistry, 2015 

The Nucleophosmin-Pin1 interaction links the cell cycle, cancer and pluripotency

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The Nucleophosmin-Pin1 interaction links the cell cycle, cancer and pluripotency

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