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Phenosafranin inhibits nuclear localization of transglutaminase 2 without affecting its transamidase activity

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Abstract

Transglutaminase 2 (TG2) localizes to the nucleus and induces apoptosis through a crosslinking inactivation of Sp1 in JHH-7 cells treated with acyclic retinoid. We screened an inhibitor suppressing transamidase activity in the nucleus without affecting transamidase activity itself. Phenosafranin was found to inhibit nuclear localization of EGFP-tagged TG2 and dose-dependently reduce nuclear transamidase activity without affecting the activity in a tube. We concluded that phenosafranin was a novel TG2 inhibitor capable of suppressing its nuclear localization.

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Abbreviations

TG:

Transglutaminase

5BAPA:

5-(Biotinamido) pentylamine

ACR:

Acyclic retinoid

DMEM:

Dulbecco’s modified Eagle medium

PBS:

Phosphate-buffered saline

NLS:

Nuclear localization signal

NES:

Nuclear export signal

NASH:

Non-alcoholic steatohepatitis

ASH:

Alcoholic steatohepatitis

Cys:

Cystamine

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Acknowledgments

We thank the former laboratory members, including Dr. Tatsukawa (currently Nagoya Univ), Ms. Fukaya-Tatsukawa, Ms. Yoshioka, and Ms. Imazawa for their efforts in an initial screening of this study. JHH-7 cells were kindly gifted by Dr. Matsuura (Jikei Univ School of Med). NPDepo chemical library was kindly gifted by Dr. Osada and Dr. Saito (RIKEN). The authors’ experimental work referred to in this report was supported in part by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan KAKENHI Grant Number JP26102742 (to SK); The Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Number JP16K09386 (to YF); Advanced Research Networks; and the Research on the Innovative Development and the Practical Application of New Drugs for Hepatitis B (Principal Investigator: SK) provided by the Agency for Medical Research and Development (AMED).

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Authors and Affiliations

  1. Micro-Signaling Regulation Technology Unit, RIKEN Center for Life Science Technologies, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan

    Yutaka Furutani, Mariko Toguchi, Rajan Shrestha & Soichi Kojima

Authors
  1. Yutaka Furutani
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  2. Mariko Toguchi
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  3. Rajan Shrestha
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  4. Soichi Kojima
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Correspondence to Soichi Kojima.

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The authors declare that they have no conflict of interest.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Handling Editors: S. Beninati, M. Piacentini, C. M. Bergamini.

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Furutani, Y., Toguchi, M., Shrestha, R. et al. Phenosafranin inhibits nuclear localization of transglutaminase 2 without affecting its transamidase activity. Amino Acids 49, 483–488 (2017). https://doi.org/10.1007/s00726-016-2337-6

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  • DOI: https://doi.org/10.1007/s00726-016-2337-6

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