Kenji Fukasawa, PhD

Our laboratory primarily focuses on elucidation of the molecular mechanism underlying genomic instability, especially that caused by numeral and functional abnormalities of centrosomes, and its relevance to carcinogenesis. Our ongoing research projects include: 1) molecular dissection of various oncogenes and tumor suppressors for their roles in the regulation of centrosome duplication and function, 2) determining how mutations in those oncogenes and tumor suppressors result in numeral as well as functional abnormalities of centrosomes, and 2) examining the diverse consequences of centrosome abnormalities and their impacts on genesis of various types of cancers.

• Ling H, Peng L, Seto E, Fukasawa K. Suppression of centrosome duplication and amplification by deacetylases. Cell Cycle. 2012 Oct;11(20):3779-3791. Pubmedid: 23022877. Pmcid: PMC3495821.
• Tarapore P, Hanashiro K, Fukasawa K. Analysis of centrosome localization of BRCA1 and its activity in suppressing centrosomal aster formation. Cell Cycle. 2012 Aug;11(15):2931-2946. Pubmedid: 22833046. Pmcid: PMC3419063.
• Peng L, Ling H, Yuan Z, Fang B, Bloom G, Fukasawa K, Koomen J, Chen J, Lane WS, Seto E. SIRT1 negatively regulates the activities, functions, and protein levels of hMOF and TIP60. Mol Cell Biol. 2012 Jul;32(14):2823-2836. Pubmedid: 22586264. Pmcid: PMC3416197.
• Reboutier D, Troadec MB, Cremet JY, Fukasawa K, Prigent C. Nucleophosmin/B23 activates Aurora A at the centrosome through phosphorylation of serine 89. J Cell Biol. 2012 Apr;197(1):19-26. Pubmedid: 22451695. Pmcid: PMC3317798.
• Peng L, Yuan Z, Ling H, Fukasawa K, Robertson K, Olashaw N, Koomen J, Chen J, Lane WS, Seto E. SIRT1 deacetylates the DNA methyltransferase 1 (DNMT1) protein and alters its activities. Mol Cell Biol. 2011 Dec;31(23):4720-4734. Pubmedid: 21947282. Pmcid: PMC3232929.
• Fukasawa K. Aberrant activation of cell cycle regulators, centrosome amplification, and mitotic defects. Horm Cancer. 2011 Apr;2(2):104-112. Pubmedid: 21761333.
• Fukasawa K. P53, cyclin-dependent kinase and abnormal amplification of centrosomes. Biochim Biophys Acta. 2008 Sep;1786(1):15-23. Pubmedid: 18472015. Pmcid: PMC2647860.
• Hanashiro K, Kanai M, Geng Y, Sicinski P, Fukasawa K. Roles of cyclins A and E in induction of centrosome amplification in p53-compromised cells. Oncogene. 2008 Sep;27(40):5288-5302. Pubmedid: 18490919.
• Fukasawa K. Oncogenes and tumour suppressors take on centrosomes. Nat Rev Cancer. 2007 Dec;7(12):911-924. Pubmedid: 18004399.
• Kanai M, Hanashiro K, Kim S, Hanai S, Boulares A, Miwa M, Fukasawa K. Inhibition of Crm1-p53 interaction and nuclear export of p53 by poly(ADP-ribosyl)ation. Nat Cell Biol. 2007 Oct;9(10):1175-1183. Pubmedid: 17891139.
• Liu X, Liu Z, Jang SW, Ma Z, Shinmura K, Kang S, Dong S, Chen J, Fukasawa K, Ye K. Sumoylation of nucleophosmin/B23 regulates its subcellular localization, mediating cell proliferation and survival. Proc Natl Acad Sci U S A. 2007 Jun;104(23):9679-9684. Pubmedid: 17535915.
• Kanai M, Ma Z, Izumi H, Kim SH, Mattison CP, Winey M, Fukasawa K. Physical and functional interaction between mortalin and Mps1 kinase. Genes Cells. 2007 Jun;12(6):797-810. Pubmedid: 17573779.
• Shinmura K, Bennett R, Tarapore P, Fukasawa K. Direct evidence for the role of centrosomally localized p53 in the regulation of centrosome duplication. Oncogene. 2007 May;26(20):2939-2944. Pubmedid: 17072342.
• Ma Z, Kanai M, Kawamura K, Kaibuchi K, Ye K, Fukasawa K. Interaction between ROCK II and nucleophosmin/B23 in the regulation of centrosome duplication. Mol Cell Biol. 2006 Dec;26(23):9016-9034. Pubmedid: 17015463. Pmcid: PMC1636820.
• Ma Z, Izumi H, Kanai M, Kabuyama Y, Ahn N, Fukasawa K. Mortalin controls centrosome duplication via modulating centrosomal localization of p53. Oncogene. 2006 Aug;25(39):5377-5390. Pubmedid: 16619038.
• Sugihara E, Kanai M, Saito S, Nitta T, Toyoshima H, Nakayama K, Nakayama KI, Fukasawa K, Schwab M, Saya H, Miwa M. Suppression of centrosome amplification after DNA damage depends on p27 accumulation. Cancer Res. 2006 Apr;66(8):4020-4029. Pubmedid: 16618721.
• Knauf JA, Ouyang B, Knudsen ES, Fukasawa K, Babcock G, Fagin JA. Oncogenic RAS induces accelerated transition through G2/M and promotes defects in the G2 DNA damage and mitotic spindle checkpoints. J Biol Chem. 2006 Feb;281(7):3800-3809. Pubmedid: 16316983.
• Tarapore P, Shinmura K, Suzuki H, Tokuyama Y, Kim SH, Mayeda A, Fukasawa K. Thr199 phosphorylation targets nucleophosmin to nuclear speckles and represses pre-mRNA processing. FEBS Lett. 2006 Jan;580(2):399-409. Pubmedid: 16376875.
• Shinmura K, Tarapore P, Tokuyama Y, George K, Fukasawa K. Characterization of centrosomal association of nucleophosmin/B23 linked to Crm1 activity. Febs Lett. 2005 Dec;579(29):6621-6634. Pubmedid: 16297385.
• Mayhew C, Bosco E, Fox S, Okaya T, Tarapore P, Schwemberger S, BabcockGF, Lentsch A, Fukasawa K, Knudsen E. Liver-specific pRB loss results in ectopic cell cycle entry and aberrant ploidy. Cancer Res. 2005 Jun;65(11):4568-4577. Pubmedid: 15930274.
• Oikawa T, Okuda M, Ma Z, Goorha R, Tsujimoto H, Inokuma H, Fukasawa K. Transcriptional control of BubR1 by p53 and suppression of centrosome amplification by BubR1. Mol Cell Biol. 2005 May;25(10):4046-4061. Pubmedid: 15870277.
• Bennett R, Izumi H, Fukasawa K. Induction of centrosome amplification and chromosome instability in p53-null cells by transient exposure to subtoxic levels of S-phase-targeting anticancer drugs. Oncogene. 2004 Sep;23(40):6823-6829. Pubmedid: 15273731.
• Kawamura K, Izumi H, Ma Z, Ikeda R, Moriyama M, Tanaka T, Nojima T, Levin L, Fujikawa-Yamamoto K, Suzuki K, Fukasawa K. Induction of centrosome amplification and chromosome instability in human bladder cancer cells by p53 mutation and cyclin E overexpression. Cancer Res. 2004 Jul;64(14):4800-4809. Pubmedid: 15256449.
• Bernard K, Litman E, Fitzpatrick J, Shellman Y, Argast G, Polvinen K, Everett A, Fukasawa K, Norris D, Ahn N, Resing K. Functional proteomic analysis of melanoma progression. Cancer Res. 2003 Oct;63(20):6716-6725. Pubmedid: 14583466.
• Forgues M, Difilippantonio MJ, Linke SP, Ried T, Nagashima K, Feden J, Valerie K, Fukasawa K, Wang XW. Involvement of Crm1 in hepatitis B virus X protein-induced aberrant centriole replication and abnormal mitotic spindles. Mol Cell Biol. 2003 Aug;23(15):5282-5292. Pubmedid: 12861014.
• Saavedra HI, Maiti B, Timmers C, Altura R, Tokuyama Y, Fukasawa K, Leone G. Inactivation of E2F3 results in centrosome amplification. Cancer Cell. 2003 Apr;3(4):333-346. Pubmedid: 12726860. Pmcid: PMC3033013.
• Kanai M, Tong WM, Sugihara E, Wang ZQ, Fukasawa K, Miwa M. Involvement of poly(ADP-Ribose) polymerase 1 and poly(ADP-Ribosyl)ation in regulation of centrosome function. Mol Cell Biol. 2003 Apr;23(7):2451-2462. Pubmedid: 12640128.
• Angus SP, Fribourg AF, Markey MP, Williams SL, Horn HF, DeGregori J, Kowalik TF, Fukasawa K, Knudsen ES. Active RB elicits late G1/S inhibition. Exp Cell Res. 2002 Jun;276(2):201-213. Pubmedid: 12027450.
• Wang Q, Xie S, Chen J, Fukasawa K, Naik U, Traganos F, Darzynkiewicz Z, Jhanwar-Uniyal M, Dai W. Cell cycle arrest and apoptosis induced by human Polo-like kinase 3 is mediated through perturbation of microtubule integrity. Mol Cell Biol. 2002 May;22(10):3450-3459. Pubmedid: 11971976. Pmcid: PMC133784.
• Tarapore P, Okuda M, Fukasawa K. A mammalian in vitro centriole duplication system: evidence for involvement of CDK2/cyclin E and nucleophosmin/B23 in centrosome duplication. Cell Cycle. 2002 Jan;1(1):75-81. Pubmedid: 12429912.
• Tarapore P, Tokuyama Y, Horn H, Fukasawa K. Difference in the centrosome duplication regulatory activity among p53 'hot spot' mutants: potential role of Ser 315 phosphorylation-dependent centrosome binding of p53. Oncogene. 2001 Oct;20(47):6851-6863. Pubmedid: 11687964.
• Tokuyama Y, Horn H, Kawamura K, Tarapore P, Fukasawa K. Specific phosphorylation of nucleophosmin on Thr(199) by cyclin-dependent kinase2-cyclin E and its role in centrosome duplication. J Biol Chem. 2001 Jun;276(24):21529-21537. Pubmedid: 11278991.
• Tarapore P, Horn H, Tokuyama Y, Fukasawa K. Direct regulation of the centrosome duplication cycle by the p53-p21Waf1/Cip1 pathway. Oncogene. 2001 May;20(25):3173-3184. Pubmedid: 11423967.
• Gustafson L, Gleich L, Fukasawa K, Chadwell J, Miller M, Stambrook P, Gluckman J. Centrosome hyperamplification in head and neck squamous cell carcinoma: a potential phenotypic marker of tumor aggressiveness. Laryngoscope. 2000 Nov;110(11):1798-1801. Pubmedid: 11081587.
• Okuda M, Horn H, Tarapore P, Tokuyama Y, Smulian A, Chan P, Knudsen E, Hofmann I, Snyder J, Bove K, Fukasawa K. Nucleophosmin/B23 is a target of CDK2/cyclin E in centrosome duplication. Cell. 2000 Sep;103(1):127-140. Pubmedid: 11051553.
• Chiba S, Okuda M, Mussman J, Fukasawa K. Genomic convergence and suppression of centrosome hyperamplification in primary p53-/- cells in prolonged culture. Exp Cell Res. 2000 Aug;258(2):310-321. Pubmedid: 10896782.
• Yamaguchi H, Okuda M, Mikala G, Fukasawa K, Varadi G. Cloning of the beta(2a) subunit of the voltage-dependent calcium channel from human heart: cooperative effect of alpha(2)/delta and beta(2a) on the membrane expression of the alpha(1C) subunit. Biochem Biophys Res Commun. 2000 Jan;267(1):156-163. Pubmedid: 10623591.
• Saavedra H, Fukasawa K, Conn C, Stambrook P. MAPK mediates RAS-induced chromosome instability. J Biol Chem. 1999 Dec;274(53):38083-38090. Pubmedid: 10608877.
• Strobeck M, Okuda M, Yamaguchi H, Schwartz A, Fukasawa K. Morphological transformation induced by activation of the mitogen-activated protein kinase pathway requires suppression of the T-type Ca2+ channel. J Biol Chem. 1999 May;274(22):15694-15700. Pubmedid: 10336467.
• Carroll P, Okuda M, Horn H, Biddinger P, Stambrook P, Gleich L, Li Y, Tarapore P, Fukasawa K. Centrosome hyperamplification in human cancer: chromosome instability induced by p53 mutation and/or Mdm2 overexpression. Oncogene. 1999 Mar;18(11):1935-1944. Pubmedid: 10208415.
• Ouyang B, Lan Z, Meadows J, Pan H, Fukasawa K, Li W, Dai W. Human Bub1: a putative spindle checkpoint kinase closely linked to cell proliferation. Cell Growth Differ. 1998 Oct;9(10):877-885. Pubmedid: 9790499 .
• Yamaguchi H, Hara M, Strobeck M, Fukasawa K, Schwartz A, Varadi G. Multiple modulation pathways of calcium channel activity by a beta subunit. Direct evidence of beta subunit participation in membrane trafficking of the alpha1C subunit. J Biol Chem. 1998 Jul;273(30):19348-19356. Pubmedid: 9668125 .
• Duesbery N, Webb C, Leppla S, Gordon V, Klimpel K, Copeland T, Ahn N, Oskarsson M, Fukasawa K, Paull K, Vande Woude G. Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor. Science. 1998 May;280(5364):734-737. Pubmedid: 9563949 .
• Fukasawa K, Wiener F, Vande Woude G, Mai S. Genomic instability and apoptosis are frequent in p53 deficient young mice. Oncogene. 1997 Sep;15(11):1295-1302. Pubmedid: 9315097 .
• Duesbery N, Choi T, Brown K, Wood K, Resau J, Fukasawa K, Cleveland D, Vande Woude G. CENP-E is an essential kinetochore motor in maturing oocytes and is masked during mos-dependent, cell cycle arrest at metaphase II. Proc Natl Acad Sci U S A. 1997 Aug;94(17):9165-9170. Pubmedid: 9256453 .
• Fukasawa K, Vande Woude G. Synergy between the Mos/mitogen-activated protein kinase pathway and loss of p53 function in transformation and chromosome instability. Mol Cell Biol. 1997 Jan;17(1):506-518. Pubmedid: 8972231 .
• Choi T, Fukasawa K, Zhou R, Tessarollo L, Borror K, Resau J, Vande Woude G. The Mos/mitogen-activated protein kinase (MAPK) pathway regulates the size and degradation of the first polar body in maturing mouse oocytes. Proc Natl Acad Sci U S A. 1996 Jul;93(14):7032-7035. Pubmedid: 8692939 .
• Choi T, Rulong S, Resau J, Fukasawa K, Matten W, Kuriyama R, Mansour S, AhnN, Vande Woude G. Mos/mitogen-activated protein kinase can induce early meiotic phenotypes in the absence of maturation-promoting factor: a novel system for analyzing spindle formation during meiosis I. Proc Natl Acad Sci U S A. 1996 May;93(10):4730-4735. Pubmedid: 8643471 .
• Fukasawa K, Choi T, Kuriyama R, Rulong S, Vande Woude G. Abnormal centrosome amplification in the absence of p53. Science. 1996 Mar;271(5256):1744-1747. Pubmedid: 8596939 .
• Fukasawa K, Zhou R, Matten W, Armstrong A, Daar I, Oskarsson M, Sathyanarayana B, Maclvor L, Wood T, Vande Woude G. Mutagenic analysis of functional domains of the mos proto-oncogene and identification of the sites important for MAPK activation and DNA binding. Oncogene. 1995 Oct;11(8):1447-1457. Pubmedid: 7478569 .
• Fukasawa K, Vande Woude G. Mos overexpression in Swiss 3T3 cells induces meiotic-like alterations of the mitotic spindle. Proc Natl Acad Sci U S A. 1995 Apr;92(8):3430-3434. Pubmedid: 7724579 .
• Resing K, Mansour S, Hermann A, Johnson R, Candia J, Fukasawa K, VandeWoude G, Ahn N. Determination of v-Mos-catalyzed phosphorylation sites and autophosphorylation sites on MAP kinase kinase by ESI/MS. Biochemistry. 1995 Feb;34(8):2610-2620. Pubmedid: 7873542 .
• Fukasawa K, Rulong S, Resau J, Pinto da Silva P, Woude G. Overexpression of mos oncogene product in Swiss 3T3 cells induces apoptosis preferentially during S-phase. Oncogene. 1995 Jan;10(1):1-8. Pubmedid: 7824263 .
• Fukasawa K, Murakami M, Blair D, Kuriyama R, Hunt T, Fischinger P, VandeWoude G. Similarities between somatic cells overexpressing the mos oncogene and oocytes during meiotic interphase. Cell Growth Differ. 1994 Oct;5(10):1093-1103. Pubmedid: 7848911 .
• Mansour S, Matten W, Hermann A, Candia J, Rong S, Fukasawa K, Vande WoudeGF, Ahn N. Transformation of mammalian cells by constitutively active MAP kinase kinase. Science. 1994 Aug;265(5174):966-970. Pubmedid: 8052857 .
• Fukasawa K, Sakoulas G, Pollack R, Chen S. Excess wild-type p53 blocks initiation and maintenance of simian virus 40 transformation. Mol Cell Biol. 1991 Jul;11(7):3472-3483. Pubmedid: 1646391 .