研究者詳細 - 嘉村　巧

論文 - 嘉村　巧

分割表示 51 件中 21 - 40 件目／全件表示 >>

Hepatic Sdf2l1 controls feeding-induced ER stress and regulates metabolism

Sasako Takayoshi, Ohsugi Mitsuru, Kubota Naoto, Itoh Shinsuke, Okazaki Yukiko, Terai Ai, Kubota Tetsuya, Yamashita Satoshi, Nakatsukasa Kunio, Kamura Takumi, Iwayama Kaito, Tokuyama Kumpei, Kiyonari Hiroshi, Furuta Yasuhide, Shibahara Junji, Fukayama Masashi, Enooku Kenichiro, Okushin Kazuya, Tsutsumi Takeya, Tateishi Ryosuke, Tobe Kazuyuki, Asahara Hiroshi, Koike Kazuhiko, Kadowaki Takashi, Ueki Kohjiro

NATURE COMMUNICATIONS 10 巻 2019年2月

Insulin-like growth factor 1 receptor stabilizes the ETV6-NTRK3 chimeric oncoprotein by blocking its KPC1/Rnf123-mediated proteasomal degradation 査読有り国際共著

Cristina E Tognon, Bo Rafn, Naniye Malli Cetinbas, Takumi Kamura, Genny Trigo, Barak Rotblat, Fumihiko Okumura, Masaki Matsumoto, Christine Chow, Monika Davare, Michael Pollak, Thibault Mayor, Poul H Sorensen

J Biol Chem 293 巻 ( 32 ) 頁： 12502 - 12515 2018年8月

The HECT-type ubiquitin ligase Tom1 contributes to the turnover of Spo12, a component of the FEAR network, in G2/M phase 査読有り

Nakatsukasa Kunio, Sone Megumi, Alemayehu Dawit Hailu, Okumura Fumihiko, Kamura Takumi

FEBS LETTERS 592 巻 ( 10 ) 頁： 1716-1724 2018年5月

Ubiquitin ligase SPSB4 diminishes cell repulsive responses mediated by EphB2 査読有り

Okumura Fumihiko, Joo-Okumura Akiko, Obara Keisuke, Petersen Alexander, Nishikimi Akihiko, Fukui Yoshinori, Nakatsukasa Kunio, Kamura Takumi

MOLECULAR BIOLOGY OF THE CELL 28 巻 ( 24 ) 頁： 3532-3541 2017年11月

Hypoxia-inducible factor-2a stabilizes the von Hippel-Lindau (VHL) disease suppressor, Myb-related protein 2 査読有り

Okumura Fumihiko, Joo-Okumura Akiko, Nakatsukasa Kunio, Kamura Takumi

PLOS ONE 12 巻 ( 4 ) 2017年4月

Subcellular Fractionation Analysis of the Extraction of Ubiquitinated Polytopic Membrane Substrate during ER-Associated Degradation. 査読有り

Nakatsukasa, K., Kamura, T.

PloS One 11 巻 ( 2 ) 頁： e0148327 2016年2月

ASB7 regulates spindle dynamics and genome integrity by targeting DDA3 for proteasomal degradation. 査読有り

Uematsu, K., Okumura, F., Tonogai, S., Okumura, AJ., Alemayehu, DH., Nishikimi, A., Fukui, Y., Nakatsukasa, K., and Kamura, T

215 巻 ( 1 ) 頁： 95-106 2016年

Parallel regulation of VHL disease by pVHL-mediated degradation of B-Myb and HIF-α. 査読有り

Okumura, F., Uematsu, K., Byrne, SD., Hirano, M., Joo-Okumura, A., Nishikimi, A., Shuin. T., Fukui, Y., Nakatsukasa, K., Kamura, T

Mol.Cell. Biol. 36 巻 ( 12 ) 頁： 1803-17 2016年

The role of cullin 5-containing ubiquitin ligases. 査読有り

Okumura, F., Okumura, AJ., Nakatsukasa, K., Kamura, T

Cell Division 2016年

The ubiquitin ligase SCFUcc1 acts as a metabolic switch for the glyoxylate cycle 査読有り

1. Nakatsukasa, K., Nishimura, T., Byrne, D., Okamoto, M., Takahashi-Nakaguchi, A., Chibana, H., Okumura, F. and Kamura, T

Molecular Cell 59 巻 ( 1 ) 頁： 22-34 2015年7月

担当区分：筆頭著者記述言語：英語掲載種別：研究論文（学術雑誌）

Despite the crucial role played by the glyoxylate cycle in the virulence of pathogens, seed germination in plants, and sexual development in fungi, we still have much to learn about its regulation. Here, we show that a previously uncharacterized SCF(Ucc1) ubiquitin ligase mediates proteasomal degradation of citrate synthase in the glyoxylate cycle to maintain metabolic homeostasis in glucose-grown cells. Conversely, transcription of the F box subunit Ucc1 is downregulated in C2-compound-grown cells, which require increased metabolic flux for gluconeogenesis. Moreover, in vitro analysis demonstrates that oxaloacetate regenerated through the glyoxylate cycle induces a conformational change in citrate synthase and inhibits its recognition and ubiquitination by SCF(Ucc1), suggesting the existence of an oxaloacetate-dependent positive feedback loop that stabilizes citrate synthase. We propose that SCF(Ucc1)-mediated regulation of citrate synthase acts as a metabolic switch for the glyoxylate cycle in response to changes in carbon source, thereby ensuring metabolic versatility and flexibility.

DOI： 10.1016/j.molcel.2015.04.013

The nutrient stress-induced small GTPase Rab5 contributes to the activation of vesicle trafficking and vacuolar activity. 査読有り

3. Nakatsukasa, K., Kanada, A., Matsuzaki, M., Byrne, SD., Okumura, F., Kamura, T

Journal of biological chemistry 289 巻 ( 30 ) 頁： 20970-20978 2014年

Integrated molecular analysis of clear-cell renal cell carcinoma 査読有り

2. Sato Y1, Yoshizato T, Shiraishi Y, Maekawa S, Okuno Y, Kamura T, Shimamura T, Sato-Otsubo A, Nagae G, Suzuki H, Nagata Y, Yoshida K, Kon A, Suzuki Y, Chiba K, Tanaka H, Niida A, Fujimoto A, Tsunoda T, Morikawa T, Maeda D, Kume H, Sugano S, Fukayama M, Aburatani H, Sanada M, Miyano S, Homma Y, Ogawa S.

Nature Genetics 45 巻 ( 8 ) 頁： 860-867 2013年8月

A stalled retrotranslocation complex reveals physical linkage between substrate recognition and proteasomal degradation during ER-associated degradation. 査読有り

Nakatsukasa K, Brodsky JL, Kamura T.

Molecular biology of the cell 24 巻 ( 11 ) 頁： 1765-1775 2013年6月

Activation of Double-stranded RNA-activated Protein Kinase (PKR) by Interferon-stimulated Gene 15 (ISG15) Modification Down-regulates Protein Translation. 査読有り

Okumura F, Okumura AJ, Uematsu K, Hatakeyama S, Zhang DE, Kamura T

Journal of biological chemistry 288 巻 ( 4 ) 頁： 2839-2847 2013年1月

Non-SCF type F-box protein Roy1/Ymr258c interacts with a Rab5-like GTPase Ypt52 and inhibits Ypt52 function. 査読有り

1. Liu, Y., Nakatsukasa, K., Kotera, M., Kanada, A., Nishimura, T., Kishi, T., Mimura, S., Kamura, T.

Mol. Biol. Cell 22 巻 ( 9 ) 頁： 1574-1584 2011年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

Skp1/Cul1/F-box (SCF)-type F-box proteins are a component of the Cullin-RING SCF ubiquitin E3 ligase, which is involved in numerous cellular processes. However, the function of non-SCF-type F-box proteins remains largely unknown. The Rab5-like small guanosine 5'-triphosphatase Vps21/Ypt51 is a key regulator of intracellular transportation; however, deletion of its isoforms, Ypt52 and Ypt53, results in only a modest inhibition of intracellular trafficking. The function of these proteins therefore remains largely elusive. Here we analyze the role of a previously uncharacterized non-SCF-type F-box protein, Roy1/Ymr258c, in cell growth and intracellular transport in Saccharomyces cerevisiae. Roy1 binds to Ypt52 under physiological conditions, and Skp1 is indispensable for the association of Roy1 with Ypt52. The vps21Δ yeast cells exhibit severe deficiencies in cell growth and intracellular trafficking, whereas simultaneous deletion of roy1 alleviates the defects caused by deletion of vps21. However, additional disruption of ypt52 in roy1Δvps21Δ cells largely suppresses the cell growth and trafficking observed in roy1Δvps21Δ cells. We demonstrate that Roy1 interacts with guanosine 5'-diphosphate-bound and nucleotide-free Ypt52 and thereby inhibits the formation of guanosine 5'-triphosphate-bound, active Ypt52. These results thus indicate that Roy1 negatively modulates cell viability and intracellular transport by suppressing Ypt52.

Cul8/Rtt101 forms a variety of protein complexes that regulate DNA damage response and transcriptional silencing 査読有り

1. Mimura, S., Yamaguchi, T., Ishii, S., Noro, E., Katsura, T., Obuse, C., Kamura, T

Journal of biological chemistry 285 巻 ( 13 ) 頁： 9858-9867 2010年3月

担当区分：筆頭著者記述言語：英語掲載種別：研究論文（学術雑誌）

The budding yeast, Saccharomyces cerevisiae, has three cullin proteins, which act as platforms for Cullin-based E3 ubiquitin ligases. Genetic evidence indicates that Cul8, together with Mms1, Mms22, and Esc4, is involved in the repair of DNA damage that can occur during DNA replication. Cul8 is thought to form a complex with these proteins, but the composition and the function of Cul8-based E3 ubiquitin ligases remain largely uncharacterized. Herein, we report a comprehensive biochemical analysis of Cul8 complexes. Cul8 was found to form a Cul8-Mms1-Mms22-Esc4 complex under physiological conditions, with Mms1 bridging Cul8 and Mms22 and Mms22 bridging Mms1 and Esc4. Domain analysis demonstrated that the N-terminal region of Mms1 and the C-terminal region of Mms22 are required for the Mms1-Mms22 interaction, whereas the N-terminal region of Mms22 is required for the Mms22-Esc4 interaction. We also found other Cul8-Mms1-binding proteins Ctf4, Esc2, and Orc5 using yeast two-hybrid screening. Esc4 and Ctf4 bound to Mms22 directly and bound to Cul8-Mms1 in the presence of Mms22, whereas Esc2 and Orc5 interacted with both Cul8 and Mms1, independently. We found that Cul8, Mms1, and Mms22 participated in the regulation of transcriptional silencing of yeast telomeres. These results suggest that Cul8-Mms1, as part of various protein complexes, is involved in the regulation of chromatin metabolism.

*SCFDia2 regulates DNA replication forks during S-phase in budding yeast. 査読有り

Mimura, S., Komata, M., Kishi, T., Shirahige, K., Kamura, T.

EMBO J. 28 巻 ( 23 ) 頁： 3693-3705 2009年12月

担当区分：筆頭著者記述言語：英語掲載種別：研究論文（学術雑誌）

Dia2 is an F-box protein, which is involved in the regulation of DNA replication in the budding yeast Saccharomyces cerevisiae. The function of Dia2, however, remains largely unknown. In this study, we report that Dia2 is associated with the replication fork and regulates replication fork progression. Using modified yeast two-hybrid screening, we have identified components of the replisome (Mrc1, Ctf4 and Mcm2), as Dia2-binding proteins. Mrc1 and Ctf4 were ubiquitinated by SCF(Dia2) both in vivo and in vitro. Domain analysis of Dia2 revealed that the leucine-rich repeat motif was indispensable for the regulation of replisome progression, whereas the tetratricopeptide repeat (TPR) motif was involved in the interaction with replisome components. In addition, the TPR motif was shown to be involved in Dia2 stability; deleting the TPR stabilized Dia2, mimicking the effect of DNA damage. ChIP-on-chip analysis illustrated that Dia2 localizes to the replication fork and regulates fork progression on hydroxyurea treatment. These results demonstrate that Dia2 is involved in the regulation of replisome activity through a direct interaction with replisome components.

*A longevity protein, Lag2, interacts with SCF complex and regulates SCF function. 査読有り

Liu, Y., Mimura, S., Kishi, T., Kamura, T.

EMBO J. 28 巻 ( 21 ) 頁： 3366-3377 2009年11月

担当区分：筆頭著者記述言語：英語掲載種別：研究論文（学術雑誌）

SCF-type E3-ubiquitin ligases control numerous cellular processes through the ubiquitin-proteasome pathway. However, the regulation of SCF function remains largely uncharacterized. Here, we report a novel SCF complex-interacting protein, Lag2, in Saccharomyces cerevisiae. Lag2 interacts with the SCF complex under physiological conditions. Lag2 negatively controls the ubiquitylation activities of SCF E3 ligase by interrupting the association of Cdc34 to SCF complex. Overexpression of Lag2 increases unrubylated Cdc53, whereas deletion of lag2, together with the deletions of dcn1 and jab1, results in the accumulation of Rub1-modified Cdc53. In vitro rubylation assays show that Lag2 inhibits the conjugation of Rub1 to Cdc53 in competition with Dcn1, which suggest that Lag2 down-regulates the rubylation of Cdc53 rather than promoting derubylation. Furthermore, Dcn1 hinders the association of Lag2 to Cdc53 in vivo. Finally, the deletion of lag2 combined with the deletion of either dcn1 or rub1 suppresses the growth of yeast cells. These observations thus indicate that Lag2 has a significant function in regulating the SCF complex by controlling its ubiquitin ligase activities and its rubylation cycle.

*Degradation of phosphorylated p53 by viral protein-ECS E3 ligase complex. 査読有り

3. Sato, Y., Kamura, T., Shirata, N., Murata, T., Kudoh, A., Iwahori, S., Nakayama, S., Isomura, H., Nishiyama, Y., Tsurumi T.

PLoS Pathog 5 巻 ( 7 ) 頁： e1000530 2009年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

p53-signaling is modulated by viruses to establish a host cellular environment advantageous for their propagation. The Epstein-Barr virus (EBV) lytic program induces phosphorylation of p53, which prevents interaction with MDM2. Here, we show that induction of EBV lytic program leads to degradation of p53 via an ubiquitin-proteasome pathway independent of MDM2. The BZLF1 protein directly functions as an adaptor component of the ECS (Elongin B/C-Cul2/5-SOCS-box protein) ubiquitin ligase complex targeting p53 for degradation. Intringuingly, C-terminal phosphorylation of p53 resulting from activated DNA damage response by viral lytic replication enhances its binding to BZLF1 protein. Purified BZLF1 protein-associated ECS could be shown to catalyze ubiquitination of phospho-mimetic p53 more efficiently than the wild-type in vitro. The compensation of p53 at middle and late stages of the lytic infection inhibits viral DNA replication and production during lytic infection, suggesting that the degradation of p53 is required for efficient viral propagation. Taken together, these findings demonstrate a role for the BZLF1 protein-associated ECS ligase complex in regulation of p53 phosphorylated by activated DNA damage signaling during viral lytic infection.

*Mammalian Elongin A complex mediates DNA-damage-induced ubiquitylation and degradation of Rpb1. 査読有り

Yasukawa T, Kamura T, Kitajima S, Conaway RC, Conaway JW, Aso T.

EMBO J. 27 巻 ( 24 ) 頁： 3256-3266 2008年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

The Elongin complex stimulates the rate of transcription elongation by RNA polymerase II (pol II) by suppressing transient pausing of the pol II at many sites along the DNA. Elongin is composed of a transcriptionally active A subunit and two small regulatory B and C subunits, which can form an isolable Elongin BC subcomplex. Here, we have shown that both the ubiquitylation and proteasomal degradation of the largest subunit of pol II (Rpb1) following UV-irradiation are significantly suppressed in Elongin A-deficient cells; however, in both cases suppression is rescued by transfection of wild-type Elongin A. Moreover, we have demonstrated that the Elongin A-Elongin BC complex is capable of assembling with the Cul5/Rbx2 module, and that this hetero-pentamer complex efficiently ubiquitylates Rpb1 in vitro. Mechanistic studies indicate that colocalization of Elongin A and Cul5 in cells and the interaction of Elongin A with the Ser5-phosphorylated form of Rpb1 are strongly enhanced following UV-irradiation. Taken together, our results suggest that mammalian Elongin A is directly involved in ubiquitylation and degradation of Rpb1 following DNA damage.

　前のページ - 次のページ　

<嘉村 巧>

論文 - 嘉村 巧

<嘉村　巧>

論文 - 嘉村　巧