Selected Publications


48 1. Hirose, Y., Kitazono, T., Sezaki, M., Abe, M., Sakimura, K., Funato, H., Handa, H., Vogt, K.E., and Yanagisawa, M. Hypnotic effect of thalidomide is independent of teratogenic ubiquitin/proteasome pathway. Proc. Natl. Acad. Sci. USA, 117, 23106-23112, 2020.
47  Cho, J., Horikawa, Y., Enya, M., Takeda, J., Imai, Y., Imai, Y., Handa, H. and Imai, T. L-Arginine prevents cereblon-mediated ubiquitination of glucokinase and stimulates glucose-6-phosphate production in pancreatic beta cells. Commun. Biol., 2020. in press 
46  Yamamoto, J., Suwa, T., Murase, Y., Tateno, S., Mizutome, H., Asatsuma-Okumura, T., Shimizu, N., Kishi, T., Momose, S., Kizaki, M., Ito, T., Yamaguchi, Y. and Handa, H. ARID2 is a pomalidomide-dependent CRL4CRBN substrate in multiple myeloma cells. Nat. Chem. Biol., 2020. in press
45 Tochigi, T., Miyamoto, T., Hatakeyama, K., Sakoda, T., Ishihara, D., Irifune, H., Shima, T., Kato, K., Maeda, T., Ito, T., Handa, H., Akashi, K. and Kikushige, Y. Aromatase is a novel neo-substrate of cereblon responsible for immunomodulatory drugs-induced thrombocytopenia. Blood, 2020. In press
44  Asakawa, K., Handa, H. and Kawakami, K. Optogenetic modulation of TDP-43 oligomerization fast-forwards ALS-related pathologies in the spinal motor neurons. Nat. Commun., 11, 1004, 2020.
43  Asatsuma-Okumura, T., Ando, H., Simone, M.D., Yamamoto, J., Sato, T., Yamaguchi, Y., Ito, T., Guerrini, L. and Handa, H. p63 is a cereblon substrate involved in thalidomide teratogenicity. Nat. Chem. Biol., 15, 1077-1084, 2019.
42 Kimura, A., Kitajima, M., Nishida, K., Serada, S., Fujimoto, M., Naka, T., Fujii-Kuriyama, Y., Sakamato, S., Ito, T., Handa, H., Tanaka, T., Yoshimura, A. and Suzuki, H. NQO1 inhibits the TLR-dependent production of selective cytokines by promoting IκB-ζ degradation. J. Exp. Med., 215, 2197-2209, 2018.
41  Matyskiela, M. E., Lu, G., Ito, T., Pagarigan, B., Lu, C-C., Miller, K., Fang, W., Wang, N-Y., Nguyen, D., Houston, J., Carmel, G., Tran, T., Riley, M., Nosaka, L., Lander, G. C., Gaidarova, S., Xu, S., Ruchelman, A. L., Handa, H., Carmichael, J., Daniel, T. O., Cathers, B. E., Lopez-Girona, A. and Chamberlain, P. P. A novel cereblon modulator recruits GSPT1 to the CRL4CRBN ubiquitin ligase. Nature, 535, 252-257, 2016.
40 Nguyen, T. V., Lee, J. E., Sweredoski, M. J., Yang, S. J., Jeon, S. J., Harrison, J. S., Yim, J. H., Lee, S. G.,　Handa, H., Kuhlman, B., Jeong, J. S., Reitsma, J. M., Park, C. S., Hess, S. and Deshaies, R. J.　Glutamine triggers acetylation-dependent degradation of glutamine　synthetase via the thalidomide receptor cereblon. Mol. Cell, 61, 809-820, 2016.
39 Kabe, Y., Nakane, T., Koike, I., Yamamoto, T., Sugiura, Y., Harada, E., Sugase, K., Shimamura, T., Ohmura, M., Muraoka, K., Yamamoto, A., Uchida, T., Iwata, S., Yamaguchi,Y., Krayukhina, E., Noda, M., Handa, H., Ishimori, K., Uchiyama, S., Kobayashi, T. and Suematsu, M. Haem-dependent dimerization of PGRMC1/sigma-2 receptor facilitates cancer proliferation and chemoresistance. Nat. Commun., 7, 11030, 2016.
38 Ito, T. and Handa, H. Myeloid disease: Another action of a thalidomide derivative.(NEWS&VIEWS) Nature, 523, 167-168, 2015.
37 Chamberlain, P., Lopez-Girona, A., Miller, K., Carmel, G., Parigan, B., Chie-Leon, B., Rychak, E., Corral, L., Ren, Y., Wang, M., Riley, M., Delker, S., Ito, T., Ando, H., Mori, T., Hirano, Y., Handa, H., Hakoshima, T., Daniel, T. and Cathers, B. Structure of the human Cerebraon-DDB1-lenalidomide complex reveals basis for responsiveness to thalidomide analogs. Nat. Struct. Mol. Biol., 21, 803-809, 2014.
36 Pérez-Perarnau, A., Preciado, S., Palmeri, C. M., Moncunill-Massaguer, C., Iglesias-Serret, D., González-Gironès, D. M., Miguel, M., Karasawa, S., Sakamoto, S., Cosialls, A. M., Rubio-Patiño, C., Saura-Esteller, J., Ramón, R., Caja, L., Fabregat, I., Pons, G., Handa, H., Albericio, F., Gil, J. and Lavilla, R. A trifluorinated thiazoline scaffold leading to pro-apoptotic agents targeting prohibitins. Angew. Chem. Int. Ed., 53, 10150-10154, 2014.
35 Yamamoto, J., Hagiwara, Y., Chiba, K., Isobe, T., Narita, T., Handa, H. and Yamaguchi, Y. DSIF and NELF interact with Integrator to specify the correct post-transcriptional fate of snRNA genes. Nat. Commun., 5, 4263, 2014.
34 Miyazaki, H., Higashimoto, K., Yada, Y., Endo, T. A., Sharif, J., Komori, T., Matsuda, M., Koseki, Y., Nakayama, M., Soejima, H., Handa, H., Koseki, H., Hirose, S. and Nishioka, K. Ash1l methylates Lys36 of histone H3 independently of transcriptional elongation to counteract Polycomf silencing. Plos Genetics, 9, e1003897, 2013.
33 Diamant, G., Amir-Zilberstein, L., Yamaguchi, Y., Handa, H. and Dikstein, R. DSIF restricts NF-kB signaling by coordinating elongation with mRNA Processing of negative feedback genes. Cell Reports, 2, 1-10, 2012.
32 Wada,T., Hara, M., Taneda, T., Qingfu, C., Takara, R., Moro, K., Takeda, K., Kishimoto, T. and Handa, H. Antisense morpholino targeting just upstream from a poly(A) tail junction of maternal mRNA removes the tail and inhibits translation. Nucleic Acids Res., 40, e173, 2012.
31 Lopez-Girona, A., Mendy, D., Ito, T., Miller, K., Gandhi, A. K., Kang, J., Karasawa, S., Carmel, G., Jackson, P., Abbasian, M., Mahmoudi, A., Cathers, B., Rychak, E., Gaidarova, S., Chen, R., Schafer, P. H., Handa, H., Daniel, T. O., Evans, J. F. and Chopra, R. Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide. Leukemia, 26, 2326-2335, 2012.
30  Ito, T., Ando, H., Suzuki, T., Ogura, T., Hotta, K., Imamura, Y., Yamaguchi, Y. and Handa, H. Identification of a primary target of thalidomide teratogenicity. Science, 327, 1345-1350, 2010.
29 Park, S. Y., Handa, H. and Sandhu, A. Magneto-optical biosensing platform based on light scattering from self-assembled chains of functionalized rotating magnetic beads. Nano Lett.,10, 446-451, 2010.
28 Chen, Y., Yamaguichi, Y., Tsugeno, Y., Yamamoto, J., Yamada, t., Nakamura, M., Hisatake, K. and Handa,H. DSIF, the Paf1 complex, and Tat-SF1 have non-redundant, cooperative roles in RNA polymerase II elongation. Genes Dev., 23, 2765-2777, 2009.
27 Kang, J., Gemberling, M., Nakamura, M., Whitby, F. G., Handa, H., Fairbrother, W. and Tantin, D. A general mechanism for transcription regulation by Oct1 and Oct4 in response to genotoxic and oxidative stress. Genes Dev., 23, 208-222, 2009.
26 Iizumi, Y., Sagara, H., Kabe, Y., Azuma, M., Kume, K., Ogawa, M., Nagai, T., Gillespie, P. G., Sasakawa, C. and Handa, H. The Enteropathogenic E.coli effector EspB facilitates microvillus effacing and –antiphagocytosis by inhibiting myosin function. Cell Host & Microbe, 2, 383-392, 2007.
25 Narita, T., Yung, T. M. C., Yamamoto, J., Tsuboi, Y., Tanabe, H., Tanaka, K., Yamaguchi, Y. and Handa, H. NELF interacts with CBC and participates in 3’-end processing of replication-dependent histone mRNAs. Mol. Cell, 26, 349-365, 2007.
24 Yamada, T., Yamaguchi, Y., Inukai, N., Kamijo, S., Mura, T. and Handa, H. P-TEFb-mediated phosphorylation of the hSpt5 C-terminal repeats is critical to processive transcription elongation. Mol. Cell, 21, 227-237, 2006.
23 Shimizu, N., Ouchida, R., Yoshikawa, N., Hisada, T., Watanabe, H., Okamoto, K., Kusuhara, M., Handa, H., Morimoto, C and Tanaka, H. HEXIM1 forms　a　transcriptionally　abortive　complex　with　glucocorticoid　receptor without　involving　7SK　RNA　and　positive　transcription elongation factor b. Proc. Natl. Acad. Sci. USA, 102, 8555-8560, 2005.
22 Jennings, B.H., Shah, S., Yamaguchi, Y., Seki, M., Phillips, R.G., Handa, H. and Ish-Horowicz, D. Locus-specific requirements for Spt5 in transcriptional activation and repression in Drosophila. Curr. Biol., 14, 1680-1684, 2004.
21 Aiyar, S.E., Sun, J-L., Blair, A.L., Moskaluk, C.A., Lu, Y.Z., Ye, Q-N., Yamaguchi, Y., Mukherjee, A., Ren, D-M., Handa, H. and Li, R.　Attenuation of estrogen receptor α-mediated transcription through estrogen-stimulated recruitment of a negative elongation factor. Genes Dev., 18,　2134-2146, 2004.
20 Mandal.　S.S, Chu, C., Wada, T., Handa, H., Shatkin, J.A. and Reinberg, D. Functional interactions of RNA-capping enzyme with factors that positively and negatively regulate promoter escape by RNA polymerase Ⅱ. Proc. Natl. Acad. Sci. USA, 101, 7572-7577, 2004.
19 Shimojima, T., Okada, M., Nakayama, T., Ueda, H., Okawa, K., Iwamatsu, A., Handa, H. and Hirose, H.Drosophila FACT contributes to Hox gene expression through physical and functional interactions with GAGA factor. Genes Dev., 17, 1605-1616, 2003.
18 Wu, C-H., Yamaguchi, Y., Benjamin, L., Horvat-Gordon, M., Washinski, J., Enerly, E., Lambertsson, A., Handa, H. and Gilmour, D. NELF and DSIF cause promoter proximal pausing on the hsp70 promoter in Drosophila. Genes Dev., 17, 1402-1414, 2003.
17 Yamaguchi, Y., Filipovska, J., Yano, K., Furuya, A., Inukai, N., Narita, T., Wada, T., Sugimoto, S., Konarska, M.M. and Handa, H. Stimulation of RNA polymerase II elongation by hepatitis delta antigen. Science, 293, 124-127, 2001.
16 Morii, E., Ogihara, H., Oboki, K., Sawa, C., Sakuma, T., Nomura, S., Esko, J.D., Handa, H. and Kitamura, Y. Inhibitory effect of the mi transcription factor encoded by the mutant mi allele on GA binding protein-mediated transcript expression in mouse mast cells. Blood, 15, 3032-3039, 2001.
15 Guo, S., Yamaguchi, Y., Schilbach, S., Wada, T., Lee, J., Goddard, A., French, D., Handa, H. and Rosenthal, A. A regulator of transcriptional elongation controls vertebrate neuronal development. Nature, 408, 366-369, 2001.
14 Shimizu, N., Sugimoto, K., Tang, J., Nishi, T., Sato, I., Hiramoto, M., Aizawa, S., Hatakeyama, M., Ohba, R., Hatori, H., Yoshikawa, T., Suzuki, F., Oomori, A., Watanabe, H., Tanaka, H., Kawaguchi, H. and Handa, H. High-performance affinity beads for identifying drug receptors. Nat. Biotechnol., 18, 877-881, 2000.
13 Wada, T., Orphanides, G., Hasegawa, J., Kim, D-K., Shima, D., Yamaguchi, Y., Fukuda, A., Hisatake, K., Oh, S., Reinberg, D. and Handa, H. FACT relieves DSIF/NELF-mediated inhibition of transcriptional elongation and reveals functional differences between P-TEFb and TFIIH. Mol. Cell, 5, 1067-1072, 2000.
12 Yamaguchi, Y., Takagi, T., Wada, T., Yano, K., Furuya, A., Sugimoto, S., Hasegawa, J. and Handa, H. NELF, a multisubunit complex containing RD, cooperates with DSIF to repress RNA polymerase II elongation. Cell, 97, 41-51, 1999.
11 Wada, T., Takagi, T., Yamaguchi, Y., Watanabe, D. and Handa, H. Evidence that p-TEFb alleviates the negative effect of DSIF on RNA polymerase II-dependent transcription in vitro. EMBO J., 17, 7395-7403, 1998.
10 Hartzog, G.A., Wada, T., Handa, H. and Winston, F. Evidence that Spt4, Spt5, and Spt6 control transcription elongation by RNA polymerase II in Saccharomyces cerevisiae. Genes Dev., 12, 357-369, 1998.
9 Wada, T., Takagi, T., Yamaguchi, Y., Ferdous, A., Imai, T., Hirose, S., Sugimoto, S., Yano, K., Hartzog, G.A., Winston, F., Buratowski, S. and Handa, H. DSIF, a novel transcription elongation factor that regulates RNA polymerase II　processivity, is composed of human Spt4 and Spt5 homologs. Genes Dev., 12, 343-356, 1998.
8 Nagata, K., Kawase, H., Handa, H., Yano, K., Yamasaki, M., Ishimi, Y., Okuda, A.,　Kikuchi, A. and Matsumoto, K. Replication factor encoded by putative oncogene,　set, associated with myeloid leukemogenesis. Proc. Natl. Acad. Sci. USA, 92,　4279-4283, 1995.
7 Sawada, J-I., Goto, M., Sawa, C., Watanabe, H. and Handa, H. Transcriptional　activation through the tetrameric complex formation of E4TF1 subunits.　EMBO J., 13, 1396-1402, 1994.
6 Ma, D., Watanabe, H., Mermelstein, F., Admon, A., Oguri, K., Sun, X., Wada, T., Imai, T., Shiroya, T., Reinberg, D. and Handa, H. Isolation of cDNA encoding the largest subunit of TFIIA reveals functions important for activated transcription.　Genes Dev., 7, 2246-2257, 1993.
5 Usuda, Y., Kubota, A., Berk, A.J. and Handa, H. Affinity-purification of transcription　factor IIA from HeLa cell nuclear extracts. EMBO J., 10, 2305-2310, 1991.
4 Mizutani, M., Ohta, T., Watanabe, H., Handa, H. and Hirose, S. Negative supercoiling　of DNA facilitates an interaction between transcription factor IID and the fibroin gene　promoter. Proc. Natl. Acad. Sci. USA, 88, 718-722, 1991.
3 Watanabe, H., Wada, T. and Handa, H. Transcription factor E4TF1 contains two subunits with different functions. EMBO J., 9, 841-847, 1990.
2 Ooyama, S., Imai, T., Hanaka, S. and Handa, H. Transcription in the reverse orientation at either terminus of the adenovirus type 5 genome. EMBO J., 8, 863-868, 1989.
1 Handa, H., Kingston, R.E. and Sharp, P.A. Inhibition of adenovirus early region IV transcription in vitro by a purified viral 72,000 DNA binding protein. Nature,　302, 545-547, 1983.