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Sak/Plk4 and mitotic fidelity

Oncogene volume 24, pages 306–312 (2005)Cite this article

Abstract

Sak/Plk4 differs from other polo-like kinases in having only a single polo box, which assumes a novel dimer fold that localizes to the nucleolus, centrosomes and the cleavage furrow. Sak expression increases gradually in S through M phase, and Sak is destroyed by APC/C dependent proteolysis. Sak-deficient mouse embryos arrest at E7.5 and display an increased incidence of apoptosis and anaphase arrest. Sak+/− mice are haploinsufficient for tumor suppression, with spontaneous tumors developing primarily in the liver with advanced age. During liver regeneration following partial hepatectomy, Sak+/− hepatocytes display a delay in reaching the first M phase, multipolar spindles, disorganized tissue morphology and loss of acuity for cyclin B1 expression. Similarly, Sak+/− MEF cells proliferate slowly, and show a high incidence of centrosome hyper-amplification. We suggest that Sak provides feedback to cell cycle regulators, and thereby precision to the switch-like transitions of centrosome duplication and exit-from-mitosis. Sak binds to p53, and studies are underway to provide a molecular context for the Sak-p53 interaction. Animal models of haploinsufficiency and more comprehensive models of cell cycle regulation should contribute to improvements in cancer risk assessment and novel therapies.

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References

  • Bai F, Pei XH, Godfrey VL and Xiong Y . (2003). Mol. Cell Biol., 23, 1269–1277.

  • Barr FA, Sillje HH and Nigg EA . (2004). Nat. Rev. Mol. Cell Biol., 5, 429–440.

  • Bell DW, Varley JM, Szydlo TE, Kang DH, Wahrer DC, Shannon KE, Lubratovich M, Verselis SJ, Isselbacher KJ, Fraumeni JF, Birch JM, Li FP, Garber JE and Haber DA . (1999). Science, 286, 2433–2434.

  • Bembenek J and Yu H . (2001). J. Biol. Chem., 276, 48237–48242.

  • Blagden SP and Glover DM . (2003). Nat. Cell Biol., 5, 505–511.

  • Brassac T, Castro A, Lorca T, Le Peuch C, Doree M, Labbe J-C and Galas S . (2000). Oncogene, 19, 3782–3790.

  • Budde PP, Kumagai A, Dunphy WG and Heald R . (2001). J. Cell Biol., 153, 149–158.

  • Dai W, Li Y, Ouyang B, Pan H, Reissmann P, Li J, Wiest J, Stambrook P, Gluckman JL, Noffsinger A and Bejarano P . (2000). Genes Chromosomes Cancer, 27, 332–336.

  • Dai W, Wang Q, Liu T, Swamy M, Fang Y, Xie S, Mahmood R, Yang YM, Xu M and Rao CV . (2004). Cancer Res., 64, 440–445.

  • Elia AE, Rellos P, Haire LF, Chao JW, Ivins FJ, Hoepker K, Mohammad D, Cantley LC, Smerdon SJ and Yaffe MB . (2003). Cell, 115, 83–95.

  • Elledge SJ . (1996). Science, 274, 1664–1672.

  • Fernebro E, Halvarsson B, Baldetorp B and Nilbert M . (2002). BMC Cancer, 2, 25.

  • Ferrell Jr JE . (2002). Curr. Opin. Cell Biol., 14, 140–148.

  • Fode C, Binkert C and Dennis JW . (1996). Mol. Cell. Biol., 16, 4665–4672.

  • Fode C, Motro B, Yousefi S, Heffernan M and Dennis JW . (1994). Proc. Natl. Acad. Sci.USA, 91, 6388–6392.

  • Hammond C, Jeffers L, Carr BI and Simon D . (1999). Hepatology, 29, 1479–1485.

  • Hartwell LH, Mortimer RK, Culotti J and Culotti M . (1973). Genetics, 74, 267–286.

  • Hudson JW, Chen L, Fode C, Binkert C and Dennis JW . (2000). Gene, 241, 65–73.

  • Hudson JW, Kozarova A, Cheung P, Macmillan JC, Swallow CJ, Cross JC and Dennis JW . (2001). Curr. Biol., 11, 441–446.

  • Initiative TA . (2000). Nature, 408, 796–815.

  • Jackson RJ, Engelman RW, Coppola D, Cantor AB, Wharton W and Pledger WJ . (2003). Cancer Res., 63, 3021–3025.

  • Knudson Jr AG . (1971). Proc. Natl. Acad. Sci. USA, 68, 820–823.

  • Lee KS, Grenfell TZ, Yarm FR and Erikson RL . (1998). Proc. Natl. Acad. Sci. USA, 95, 9301–9306.

  • Leung GC, Hudson JW, Kozarova A, Davidson A, Dennis JW and Sicheri F . (2002). Nat. Struct. Biol., 9, 719–724.

  • Lindon C and Pines J . (2004). J. Cell Biol., 164, 233–241.

  • Lu T, Pan Y, Kao SY, Li C, Kohane I, Chan J and Yankner BA . (2004). Nature, 429, 883–891.

  • Lucas JA, Miller AT, Atherly LO and Berg LJ . (2003). Immunol. Rev., 191, 119–138.

  • Ly DH, Lockhart DJ, Lerner RA and Schultz PG . (2000). Science, 287, 2486–2492.

  • Macmillan JC, Hudson JW, Bull S, Dennis JW and Swallow CJ . (2001). Ann. Surg. Oncol., 8, 729–740.

  • Malkin D, Li FP, Strong LC, Fraumeni Jr JF, Nelson CE, Kim DH, Kassel J, Gryka MA, Bischoff FZ and Tainsky MA . (1990). Science, 250, 1233–1238.

  • McNally KP, Buster D and McNally FJ . (2002). Cell Motil. Cytoskeleton, 53, 337–349.

  • Michel LS, Liberal V, Chatterjee A, Kirchwegger R, Pasche B, Gerald W, Dobles M, Sorger PK, Murty VVVS and Benezra R . (2001). Nature, 409, 355–359.

  • Muraoka RS, Lenferink AE, Law B, Hamilton E, Brantley DM, Roebuck LR and Arteaga CL . (2002). Mol. Cell. Biol., 22, 2204–2219.

  • Ouyang B, Pan H, Lu L, Li J, Stambrook P, Li B and Dai W . (1997). J. Biol. Chem, 272, 28646–28651.

  • Philipp-Staheli J, Payne SR and Kemp CJ . (2001). Exp. Cell Res., 264, 148–168.

  • Sharon G and Simchen G . (1990). Genetics, 125, 475–485.

  • Sherr CJ . (2004). Cell, 116, 235–246.

  • Shirayama M, Zachariae W, Ciosk R and Nasmyth K . (1998). EMBO J., 17, 1336–1349.

  • Sigrist SJ and Lehner CF . (1997). Cell, 90, 671–681.

  • Simizu S and Osada H . (2000). Nat. Cell Biol., 2, 852–854.

  • Su TT, Sprenger F, DiGregorio PJ, Campbell SD and O’Farrell PH . (1998). Genes Dev., 12, 1495–1503.

  • Takahashi T, Sano B, Nagata T, Kato H, Sugiyama Y, Kunieda K, Kimura M, Okano Y and Saji S . (2003). Cancer Sci., 94, 148–152.

  • Tarapore P and Fukasawa K . (2002). Oncogene, 21, 6234–6240.

  • Tarapore P, Okuda M and Fukasawa K . (2002). Cell Cycle, 1, 75–81.

  • Tsai KY, MacPherson D, Rubinson DA, Nikitin AY, Bronson R, Mercer KL, Crowley D and Jacks T . (2002). Proc. Natl. Acad. Sci. USA, 99, 16865–16870.

  • Visintin R, Stegmeier F and Amon A . (2003). Mol. Biol. Cell, 14, 4486–4498.

  • Wolf G, Elez R, Doermer A, Holtrich U, Ackermann H, Stutte HJ, Altmannsberger H-M, Rubsamen-Waigmann H and Strebhardt K . (1997). Oncogene, 14, 543–549.

  • Xiong W and Ferrell Jr JE . (2003). Nature, 426, 460–465.

  • Yamashita Y, Kajigaya S, Yoshida K, Ueno S, Ota J, Ohmine K, Ueda M, Miyazato A, Ohya K, Kitamura T, Ozawa K and Mano H . (2001). J. Biol. Chem., 276, 39012–39020.

  • Yarm FR . (2002). Mol. Cell. Biol., 22, 6209–6221.

  • Zhang H, Shi X, Paddon H, Hampong M, Dai W and Pelech S . (2004). J. Biol. Chem, 279, 35726–35734.

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Acknowledgements

This research was supported by a grant from the National Cancer Institute of Canada to JWD and from the National Colorectal Cancer Campaign to CJS. We thank Jennifer C Macmillan and Carla Rosario for technical contributions.

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Authors and Affiliations

  1. Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Ave. R988, Toronto, Ontario, Canada, M5G 1X5

    Carol J Swallow, Michael A Ko, Najeeb U Siddiqui & James W Dennis

  2. Department of Surgery, University of Toronto, Ontario, Canada

    Carol J Swallow & Michael A Ko

  3. Department of Microbiology and Medical Genetics, University of Toronto, Ontario, Canada

    Najeeb U Siddiqui & James W Dennis

  4. Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada

    Najeeb U Siddiqui & James W Dennis

  5. Department of Biological Sciences, University of Windsor, Ontario, Canada

    John W Hudson

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Correspondence to James W Dennis.

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Swallow, C., Ko, M., Siddiqui, N. et al. Sak/Plk4 and mitotic fidelity. Oncogene 24, 306–312 (2005). https://doi.org/10.1038/sj.onc.1208275

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