A fundamental requirement of the cell division cycle is the maintenance, replication, and segregation of chromosomal DNA, the specific order of which is ensured by checkpoints. Dr. Kitagawa is interested in the role that the spindle checkpoint plays in tumor development. Mutations in genes required for kinetochore function and mitotic checkpoint surveillance possibly contribute development of cancer.
The Kitagawa Lab is employing a series of genetic and biochemical strategies to identify additional interacting gene products, regulators, and potential substrates of Sgt1/Skp1/Hsp90 action in yeast and vertebrates. In studies with human cells, Dr. Kitagawa has found a novel mechanism by which 17-AAG (an Hsp90 inhibitor and a novel anti-cancer drug) inhibits cell proliferation and provide the first evidence of HSP90 being required for assembly of kinetochore protein complexes in humans. Other projects include studying the relationship between mitotic cell death and the spindle checkpoint, and the role of the mitotic cell death in tumorigenesis using mouse models.
Lab Web Site: http://www.nationwidechildrens.org/k-kitagawa-lab
Ohkuni,Kentaro; Kitagawa,Katsumi. 2012. Role of transcription at centromeres in budding yeast. Transcription. Vol. 3, no. 4. (July): 193-197.
Yang C; Tang X; Guo X; Niikura Y; Kitagawa K; Cui K; Wong ST; Fu L; Xu B. 2011. Aurora-B Mediated ATM Serine 1403 Phosphorylation Is Required for Mitotic ATM Activation and the Spindle Checkpoint. Molecular Cell. Vol. 44, no. 4. (November): e597.
Ohkuni K; Kitagawa K. 2011. Endogenous transcription at the centromere facilitates centromere activity in budding yeast. Current Biology: CB. Vol. 21, no. 20. (October): e1695.
Kitagawa K. 2011. Too early to say, "no targeting of mitosis!". Nature Reviews. Clinical Oncology. Vol. 8, no. 7. (May): e444; author reply 444.
Goto,Greicy,H; Mishra,Ashutosh; Abdulle,Rashid; Slaughter,Clive,A; Kitagawa,Katsumi. 2011. Bub1-Mediated Adaptation of the Spindle Checkpoint. PLOS GENETICS. Vol. 7, no. 1. (January): ee1001282.
Goto GH, Mishra A, Abdulle R, Slaughter CA, and Kitagawa K. Bub1-mediated Adaptation of the Spindle Checkpoint. PLoS Genetics, in press.
Kikuchi,Koji; Niikura,Yohei; Kitagawa,Katsumi; Kikuchi,Akira. 2010. Dishevelled, a Wnt signalling component, is involved in mitotic progression in cooperation with Plk1. EMBO JOURNAL. Vol. 29, no. 20. (October): 3470-3483.
Niikura Y; Ogi H; Kikuchi K; Kitagawa K. 2010. BUB3 that dissociates from BUB1 activates caspase-independent mitotic death (CIMD). Cell Death And Differentiation. Vol. 17, no. 6. (June): e1011.
Kikuchi K, Niikura Y, Kitagawa K, Kikuchi A.Dishevelled, a Wnt signalling component, is involved in mitotic progression in cooperation with Plk1.EMBO J. 2010 Oct 20;29(20):3470-83.
Kitagawa, Katsumi. 2009. Caspase-Independent Mitotic Death. In Essentials of Apoptosis, Second Edition:A GUIDE FOR BASIC AND CLINICAL RESEARCH.: HUMANA PRESS INC.
Bansal PK, Mishra A. High AA. Abdulle R. Kitagawa K. Sgtl dimerization is negatively regulated by protein kinase CK2-mediated phosphorylation at S361; J Biol Chem. 2009 Jul 10;284(28):18692-8.
Bansal PK. Nourse A. Abdulle R, Kitagawa K. Sgtl dimerization is required for yeast kinetochore assembly. J Biol Chem 2009; 284(6):3586-92.
Ohkuni,Kentaro; Abdulle,Rashid; Tong,Amy,Hin Yan; Boone,Charles; Kitagawa,Katsumi. 2008. Ybp2 Associates with the Central Kinetochore of Saccharomyces cerevisiae and Mediates Proper Mitotic Progression. PLOS ONE. Vol. 3, no. 2. (February): ee1617.
Kitagawa K and Niikura Y. Caspase-Independent Mitotic Death (CIMD). Cell Cycle. 2008; 7(8): 1001-5.
Ohkuni K. Abdulle R, Tong AH, Boone C, and Kitagawa K. Ybp2 Associates with the Central Kinetochore of Saccharomyces cerevjsi.ae and Mediates Proper Mitotic Progression. PLoS ONE. 2008;3(2):e1617.
Niikura,Yohei; Dixit,Amruta; Scott,Ray; Perkins,Guy; Kitagawa,Katsumi. 2007. BUB1 mediation of caspase-independent mitotic death determines cell fate. JOURNAL OF CELL BIOLOGY. Vol. 178, no. 2. (July): 283-296.
Scaglione KM, Bansal PK, Deffenbaugh AE, Kiss A, Moore 1M, Korolev S, Cocklin R, GoebJ M , Kitagawa K, and Skowyra D. SCF E3 -mediated autoubiquitination negatively regulates activity of the Cdc34 E2 but plays a nonessential role in the catalytic cycle in vitro and in vivo . Mol. Cell. Biol. 2007;27(16):5860-70.
Niikura Y, Dixit A, Scott R, Perkins G and Kitagawa K. BUB 1 mediation of caspase-independent mitotic death determines cell fate . J. Cell Biol. 2007;178(2):283-96.
Niikura Y; Ohta S; Vandenbeldt KJ; Abdulle R; McEwen BF; Kitagawa K. 2006. 17-AAG, an Hsp90 inhibitor, causes kinetochore defects: a novel mechanism by which 17-AAG inhibits cell proliferation. Oncogene. Vol. 25, no. 30. (July): e4133.
Kondo-Okamoto N, Ohkuni K, Kitagawa K, McCaffery 1M, Shaw 1M, Okamoto K. The novel F-box protein Mfb1 p regulates mitochondrial connectivity and exhibits asymmetric localization in yeast. Mol. Bioi. Cell 2006; 17:3756-67.
Niikura Y, Ohta S, Vandenbeldt K1, Abdulle R, McEwen BFand Kitagawa K. 17-AAG. an Hsp90 inhibitor, causes kinetochore defects: a novel mechanism by which 17-AAG inhibits cell proliferation. Oncogene 2006; 25:4133-46.
Bansal,P,K; Abdulle,R; Kitagawa,K. 2004. Sgt1 associates with Hsp90: an initial step of assembly of the core kinetochore complex. MOLECULAR AND CELLULAR BIOLOGY. Vol. 24, no. 18. (September): 8069-8079.
Steensgaard P, Garre M, Muradore I, Transidico P, Nigg EA, Kitagawa K, Earnshaw WC, Faretta M, Musacchio A. Sgt1 is required for human kinetochore assembly. EMBO Rep. 2004 1un;5(6):626-31.
Bansal PK, Abdulle R, and Kitagawa K. Sgt1 associates with molecular chaperones: an initial step of assembly of the core kinetochore complex. Mol. Cell. Biol. 2004 Sep;24(18):8069-79.
Niikura,Y; Kitagawa,K. 2003. Identification of a novel splice variant: Human SGT1B (SUGT1B). DNA SEQUENCE. Vol. 14, no. 6. (December): 436-441.
Kitagawa,K; Abdulle,R; Bansal,P,K; Cagney,G; Fields,S; Hieter,P. 2003. Requirement of Skp1-Bub1 interaction for kinetochore- mediated activation of the spindle checkpoint. MOLECULAR CELL. Vol. 11, no. 5. (May): 1201-1213.
Kitagawa K, Abdulle R, Bansal PK, Cagney G, Fields S, and Hieter P. Requirement of Skp 1-Bub 1 interaction for kinetochore-mediated activation of the spindle checkpoint. Mol. Cell. 2003 May; II (5): 1201-13.
Nowotny M, Spiechowicz M,Jastrzebska S, Filipek A, Kitagawa K, Kuznicki 1. Calcium-regulated interaction of Sgtl with SlOOA6 (calcyclin) and other S100 proteins. J. Biol. Chem. 2003 Jul 18;278(29):26923-8 .
Niikura Y and Kitagawa K. Identification of a Novel Splice Variant: Human SGT1B (SUGT1B). DNA sequence. 2003 Dec;14(6):436-41.
Katsumi Kitagawa. 2003. Caspase-Independent Mitotic Death. Totowa: Humana Press.
Kitagawa,K; Abdulle,R. 2002. In vivo site-directed mutagenesis of yeast plasmids using a three-fragment homologous recombination system. BIOTECHNIQUES. Vol. 33, no. 2. (August): 288-?.
AzevedQ C, Sadanandom A, Kitagawa K, Freialdenhoven A., ShirasLJ K, and Schulze-Lefert P. The RARI interactor SGT1 , an essential component of R gene-triggered disease resistance. Science. 2002 Mar 15;295(5562):2073-76.
Kitagawa K and Abdulle R. In vivo site-directed mutagenesis of yeast plasmids by using a three-fragment homologous recombination system. Biotechniques. 2002 Aug;33(2):288, 290, 292 passim.
Schadick KH, Fourcade M, Boumenot P, Seitz JJ, Morrell JL, Chang L, Gould KL, Partridge JF, Allshire RC, Kitagawa K, Bieter P, and Hoffman CS. Schizosucchurumyc;espombe Git7p, a member of the Saccharomyces cerevisiae Sgtl p family, is required for Pglucose/cAMP signaling, cell wall integrity, and septation. Eukaryot Cell. 2002 Aug;1 (4):558-67.
Dubacq C, Gucrois R, Courbcyrctte R, Kitagawa K, and Mann C. Sgt1p contributes to cAMP pathway activity and physically interacts with the adenylyl cyclase Cyrlp/Cdc35p in budding yeast. Eukaryot Cell. 2002 Aug;1 (4):568-82.
Kitagawa K and Hieter P. Evolutionary conservation between budding yeast and human kinetochores. Nature Reviews Mol. Cel. Bioi. 2001 Sep;2 (9):678-87. Review .
Kitagawa K, Skowyra D, Elledge Sl, Harper lW, and Hieter P. SeTl encodes an essential component of the yeast kinetochore assembly pathway and a novel subunit of the SCF ubiquitin ligase complex. Mol. Cell. 1999 lui; 4(1): 21-33.
Iwahara J, Kigawa T, Kitagawa K, Masumoto H, Okazaki T, and Yokoyama S. A helix-tum-helix structure unit in human centromere protein B (CENP-B). EMBO. 1998 Feb 2;17(3):827-37.
Bassett DE Jr; Basrai MA; Connelly C; Hyland KM; Kitagawa K; Mayer ML; Morrow DM; Page AM; Resto VA; Skibbens RV; Hieter P. 1996. Exploiting the complete yeast genome sequence. Current Opinion In Genetics & Development. Vol. 6, no. 6. (December): e763.
Bassett DE Jr, Basrai MA, Connelly C, Hyland KM , Kitagawa K, Mayer ML, Morrow DM, Page AM, Restro VA, Skibbens RV, and Hieter P. Exploiting the complete yeast genome sequence. Curr Opin. Genet. Dev. 1996 Dec; 6(6):763-6.
Yoda K, Nakamura T, Masumoto H, Suzuki N, Kitagawa K, Nakano M, Shinjo A, and Okazaki T. Centromere protein B of African green monkey cells: gene structure, cellular expression, and centromeric localization. Mol. Cell. Biol. 1996 Sep;16(9):5169-77
Kitagawa K, Masumoto H, Ikeda M, and Okazaki T. Analysis of protein-DNA and protein-protein interactions of centromere protein B (CENP-B) and properties of the DNA-CENP-B complex in the cell cycle. Mol. Cell. Biol. 1995 Mar;15(3): 1602-12.
Katsumi Kitagawa. 1995. Analysis of protein-DNA and protein-protein interactions of centromere protein B (CENP-B). Nagoya, Japan: Nagoya University.
Seki N, Saito T, Kitagawa K, Masumoto H, Okazaki T, and Hori T. Mapping of the human centromere protein B (CENPB) to chromosome 20p13 by fluorescence in situ hybridization. Genomics. 1994 Nov 1 ;24(1): 187-8.
Yoda K. Kitagawa K, Masutnoto H, Muro Y t and Okazaki T , A human centromere protein, CENP-B, ha!'l a DNA binding domain containing four potential a helices at the NH2 terminus, which is separable from dimerizing activity. J. Cell Biol. 1992 Dec; 119(6): 1413-27.