Graduate School of Biological Sciences KATO LAB

Contact

Nara Institute of Science and Technology
Graduate School of Science and Technology 
Division of Biological Science
Laboratory of Tumor Cell Biology (KATO LAB)

8916-5 Takayama, Ikoma, Nara 630-0101, Japan
Phone: +81-743-72-5510
Fax: +81-743-72-5519

Key Words

Cell Cycle, G1 Progression, Tumorigenesis, Hematopoiesis, Leukemogenesis, Cancer Research, Cancer Metabolism, ROS Regulation, Lipid Metabolism

Staff

Jun-ya Kato 
Noriko Kato 
Ikuko Nakamae
Hidenori Ito

About our Laboratory

Our research focuses on the molecular mechanisms that control tumor cell proliferation, differentiation, and survival. Areas of research include cell cycle control, cell differentiation, cancer metabolism, stem cell control, and apoptosis. Research in these areas help in the characterization of tumor cells and has applications in cancer diagnosis, treatment, and regenerative medicine. We use the following experimental systems in our research: (1) in vitro culture system using mouse and human cell lines, and (2) in vivo mouse model system using knockout mice and transgenic mice.

Research Areas

Research Summary

Focusing on the molecular mechanisms that control the proliferation, differentiation, and death of mammalian cells, we are conducting research on the regulation of the G1 phase of the cell cycle and carcinogenesis, and on the differentiation, proliferation, and tumorigenesis of hematopoietic stem cells and blood cells. The results will be useful for regenerative medicine and cancer research. Experimental systems that we use include (1) in vitro cell cultures of mouse and human cell lines, (2) in vitro induction of differentiation using ES cells, and (3) in vivo mouse models using knockout mice and transgenic mice.

Main Research Fields

1. Cell cycle control and carcinogenesis
   - Identification and functional analysis of the upstream regulators of G1 regulators.
2. Hematopoiesis and blood cell differentiation・Proliferation・Carcinogenesis
   - Identification of genes whose products influence hematopoiesis. 
   - Analysis of their involvement in human hematopoietic malignancies.
3. Cell carcinogenesis
   - Identification of genetic abnormalities in cell cycle regulator genes.
4. Analysis using mouse models
5. COP9 signalosome
   - Molecular function of the mammalian COP9 signalosome complex
6. Cancer metabolism
   - Regulation of ROS
   - Anti-oxidant system in cancer (GSH and TXN)
   - Curcumin (anti-tumorigeniuc activity)
   - Curcumin analogs

Publications

Curcumin Derivatives Verify the Essentiality of ROS Upregulation in Tumor Suppression.
Nakamae I, Morimoto T, Shima H, Shionyu M, Fujiki H, Yoneda-Kato N, Yokoyama T, Kanaya S, Kakiuchi K, Shirai T, Meiyanto E, Kato JY.
Molecules. 2019 Nov 10;24(22). pii: E4067. doi: 10.3390/molecules24224067.

Pentagamavunon-1 (PGV-1) inhibits ROS metabolic enzymes and suppresses tumor cell growth by inducing M phase (prometaphase) arrest and cell senescence.
Lestari B, Nakamae I, Yoneda-Kato N, Morimoto T, Kanaya S, Yokoyama T, Shionyu M, Shirai T, Meiyanto E, Kato JY.
Sci Rep. 2019 Oct 16;9(1):14867. doi: 10.1038/s41598-019-51244-3.

Cell cycle modulation of CHO-K1 cells under Genistein treatment correlates with cells senescence, apoptosis and ROS level but in a dose-dependent manner.
Jenie RI, Amalina ND, Ilmawati GPN, Utomo RY, Ikawati M, Kato JY,Meiyanto E.
Advanced Pharmaceutical Bulletin, 2019, 9(3):453-461.

Anti-Proliferative and Anti-Metastatic Potential of Curcumin Analogue, Pentagamavunon-1 (Pgv-1), Toward Highly Metastatic Breast Cancer Cells in Correlation With Ros Generation.
Meiyanto E, Putri H, Arum Larasati Y, Yudi Utomo R, Jenie RI, Ikawati M, Lestari B, Yoneda-Kato N, Nakamae I, Kawaichi M, Kato JY.
Advanced Pharmaceutical Bulletin, 2019, 9(3):445-452. 

Curcumin targets multiple enzymes involved in the ROS metabolic pathway to suppress tumor cell growth.
Larasati YA, Yoneda-Kato N, Nakamae I, Yokoyama T, Meiyanto E, Kato JY.
Sci Rep. 2018 Feb 1;8(1):2039. doi: 10.1038/s41598-018-20179-6.
Myeloid leukemia factor 1 stabilizes tumor suppressor C/EBPα to prevent Trib1-driven acute myeloid leukemia.
Nakamae I, Kato JY, Yokoyama T, Ito H, Yoneda-Kato N.
Blood Adv. 2017 Sep 1;1(20):1682-1693. doi: 10.1182/bloodadvances.2017007054. eCollection 2017 Sep 12.

Homozygous inactivation of CHEK2 is linked to a familial case of multiple primary lung cancer with accompanying cancers in other organs.
Kukita Y, Okami J, Yoneda-Kato N, Nakamae I, Kawabata T, Higashiyama M, Kato J, Kodama K, Kato K.
Cold Spring Harb Mol Case Stud. 2016 Nov;2(6):a001032.

COP1 targets C/EBPα for degradation and induces acute myeloid leukemia via Trib1.
Yoshida A, Kato JY, Nakamae I, Yoneda-Kato N.
Blood. 2013 Sep 5; 122(10):1750-60. doi: 10.1182/blood-2012-12-476101. Epub 2013 Jul 24.

CSN5 specifically interacts with CDK2 and controls senescence in a cytoplasmic cyclin E-mediated manner.
Yoshida A, Yoneda-Kato N, Kato JY.
Sci Rep. 2013; 3:1054. doi: 10.1038/srep01054. Epub 2013 Jan 11.

The COP1 E3-ligase interacts with FIP200, a key regulator of mammalian autophagy.
Kobayashi S, Yoneda-Kato N, Itahara N, Yoshida A, Kato JY.
BMC Biochem. 2013 Jan 6;14:1. doi: 10.1186/1471-2091-14-1.

Depletion of CSN5 inhibits Ras-mediated tumorigenesis by inducing premature senescence in p53-null cells.
Tsujimoto I, Yoshida A, Yoneda-Kato N, Kato JY.
FEBS Lett. 2012 Dec 14;586(24):4326-31. doi: 10.1016/j.febslet.2012.10.042. Epub 2012 Nov 2.

New twist in the regulation of cyclin D1.
Kato JY, Yoneda-Kato N.
Biomol Concepts. 2010 Dec 1;1(5-6):403-9. doi: 10.1515/bmc.2010.029.

CSN5/Jab1 controls multiple events in the mammalian cell cycle.
Yoshida A, Yoneda-Kato N, Panattoni M, Pardi R, Kato JY.
FEBS Lett. 2010 Nov 19;584(22):4545-52. doi: 10.1016/j.febslet.2010.10.039. Epub 2010 Oct 26.

Kato JY, Sherr CJ. (1993) Inhibition of granulocyte differentiation by G1 cyclins D2 and D3 but not D1. Proc Natl Acad Sci U S A, 90, 11513-7.

Kato J, Matsushime H, Hiebert SW, Ewen ME, Sherr CJ. (1993) Direct binding of cyclin D to the retinoblastoma gene product (pRb) and pRb phosphorylation by the cyclin D-dependent kinase CDK4. Genes Dev, 7, 331-42.

Quelle DE, Ashmun RA, Shurtleff SA, Kato JY, Bar-Sagi D, Roussel MF, Sherr CJ. (1993) Overexpression of mouse D-type cyclins accelerates G1 phase in rodent fibroblasts. Genes Dev, 7, 1559-71.

Kato JY, Matsuoka M, Polyak K, Massague J, Sherr CJ. (1994) Cyclic AMP-induced G1 phase arrest mediated by an inhibitor (p27Kip1) of cyclin-dependent kinase 4 activation. Cell, 79, 487-96.

Kato JY, Matsuoka M, Strom DK, Sherr CJ. (1994) Regulation of cyclin D-dependent kinase 4 (cdk4) by cdk4-activating kinase. Mol Cell Biol, 14, 2713-21.

Matsushime H, Quelle DE, Shurtleff SA, Shibuya M, Sherr CJ, Kato JY. (1994) D-type cyclin-dependent kinase activity in mammalian cells. Mol Cell Biol, 14, 2066-76.

Polyak K, Kato JY, Solomon MJ, Sherr CJ, Massague J, Roberts JM, Koff A. (1994) p27Kip1, a cyclin-Cdk inhibitor, links transforming growth factor-beta and contact inhibition to cell cycle arrest. Genes Dev, 8, 9-22.

Kitagawa M, Higashi H, Jung HK, Suzuki-Takahashi I, Ikeda M, Tamai K, Kato J, Segawa K, Yoshida E, Nishimura S, Taya Y. (1996) The consensus motif for phosphorylation by cyclin D1-Cdk4 is different from that for phosphorylation by cyclin A/E-Cdk2. Embo J, 15, 7060-9.

Kurokawa K, Tanaka T, Kato J. (1999) p19ARF prevents G1 cyclin-dependent kinase activation by interacting with MDM2 and activating p53 in mouse fibroblasts. Oncogene, 18, 2718-27.

Tomoda K, Kubota Y, Kato J. (1999) Degradation of the cyclin-dependent-kinase inhibitor p27Kip1 is instigated by Jab1. Nature, 398, 160-5.

Yoneda-Kato N, Fukuhara S, Kato J. (1999) Apoptosis induced by the myelodysplastic syndrome-associated NPM-MLF1 chimeric protein. Oncogene, 18, 3716-24.

Yoneda-Kato, N., Tomoda, K., Umehara, M., Arata, Y., and Kato, J. Y.. Myeloid leukemia factor 1 regulates p53 by suppressing COP1 via COP9 signalosome subunit 3. EMBO J. 24: 1739-1749, 2005.

Yoneda-Kato, N., Kato, J.Y. Shuttling imbalance of MLF1 results in p53 instability and increases susceptibility to oncogenic transformation. Mol Cell Biol. 28: 422-434, 2008.

Kato JY, and Yoneda-Kato N. Mammalian COP9 signalosome. (Review) Genes to Cells 14: 1209-25, 2009.

CSN5 specifically interacts with CDK2 and controls senescence in a cytoplasmic cyclin E-mediated manner.
Yoshida A, Yoneda-Kato N, Kato JY.
Sci Rep. 2013;3:1054. doi: 10.1038/srep01054. Epub 2013 Jan 11.

COP1 targets C/EBPα for degradation and induces acute myeloid leukemia via Trib1.
Yoshida A, Kato JY, Nakamae I, Yoneda-Kato N.
Blood. 2013 Sep 5;122(10):1750-60. doi: 10.1182/blood-2012-12-476101. Epub 2013 Jul 24.

Myeloid leukemia factor 1 stabilizes tumor suppressor C/EBPα to prevent Trib1-driven acute myeloid leukemia.
Nakamae I, Kato JY, Yokoyama T, Ito H, Yoneda-Kato N.
Blood Adv. 2017 Sep 1;1(20):1682-1693. doi: 10.1182/bloodadvances.2017007054. eCollection 2017 Sep 12.

Larasati YA, Yoneda-Kato N, Nakamae I, Yokoyama T, Meiyanto E, Kato JY. Curcumin targets multiple enzymes involved in the ROS metabolic pathway to suppress tumor cell growth. Sci Rep. 2018 Feb 1;8(1):2039. doi: 10.1038/s41598-018-20179-6.

 

 
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