Tryptophanemia is controlled by a tryptophan-sensing mechanism ubiquitinating tryptophan 2,3-dioxygenase

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Tryptophanemia is controlled by a tryptophan-sensing mechanism ubiquitinating tryptophan 2,3-dioxygenase. / Klaessens, Simon; Stroobant, Vincent; Hoffmann, Delia; Gyrd-Hansen, Mads; Pilotte, Luc; Vigneron, Nathalie; De Plaen, Etienne; Van den Eynde, Benoit J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 118, No. 23, 2021, p. e2022447118.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Klaessens, S, Stroobant, V, Hoffmann, D, Gyrd-Hansen, M, Pilotte, L, Vigneron, N, De Plaen, E & Van den Eynde, BJ 2021, 'Tryptophanemia is controlled by a tryptophan-sensing mechanism ubiquitinating tryptophan 2,3-dioxygenase', Proceedings of the National Academy of Sciences of the United States of America, vol. 118, no. 23, pp. e2022447118. https://doi.org/10.1073/pnas.2022447118

APA

Klaessens, S., Stroobant, V., Hoffmann, D., Gyrd-Hansen, M., Pilotte, L., Vigneron, N., De Plaen, E., & Van den Eynde, B. J. (2021). Tryptophanemia is controlled by a tryptophan-sensing mechanism ubiquitinating tryptophan 2,3-dioxygenase. Proceedings of the National Academy of Sciences of the United States of America, 118(23), e2022447118. https://doi.org/10.1073/pnas.2022447118

Vancouver

Klaessens S, Stroobant V, Hoffmann D, Gyrd-Hansen M, Pilotte L, Vigneron N et al. Tryptophanemia is controlled by a tryptophan-sensing mechanism ubiquitinating tryptophan 2,3-dioxygenase. Proceedings of the National Academy of Sciences of the United States of America. 2021;118(23):e2022447118. https://doi.org/10.1073/pnas.2022447118

Author

Klaessens, Simon ; Stroobant, Vincent ; Hoffmann, Delia ; Gyrd-Hansen, Mads ; Pilotte, Luc ; Vigneron, Nathalie ; De Plaen, Etienne ; Van den Eynde, Benoit J. / Tryptophanemia is controlled by a tryptophan-sensing mechanism ubiquitinating tryptophan 2,3-dioxygenase. In: Proceedings of the National Academy of Sciences of the United States of America. 2021 ; Vol. 118, No. 23. pp. e2022447118.

Bibtex

@article{f800a147a95d4ca581bfc8c5e36b9265,
title = "Tryptophanemia is controlled by a tryptophan-sensing mechanism ubiquitinating tryptophan 2,3-dioxygenase",
abstract = "Maintaining stable tryptophan levels is required to control neuronal and immune activity. We report that tryptophan homeostasis is largely controlled by the stability of tryptophan 2,3-dioxygenase (TDO), the hepatic enzyme responsible for tryptophan catabolism. High tryptophan levels stabilize the active tetrameric conformation of TDO through binding noncatalytic exosites, resulting in rapid catabolism of tryptophan. In low tryptophan, the lack of tryptophan binding in the exosites destabilizes the tetramer into inactive monomers and dimers and unmasks a four-amino acid degron that triggers TDO polyubiquitination by SKP1-CUL1-F-box complexes, resulting in proteasome-mediated degradation of TDO and rapid interruption of tryptophan catabolism. The nonmetabolizable analog alpha-methyl-tryptophan stabilizes tetrameric TDO and thereby stably reduces tryptophanemia. Our results uncover a mechanism allowing a rapid adaptation of tryptophan catabolism to ensure quick degradation of excess tryptophan while preventing further catabolism below physiological levels. This ensures a tight control of tryptophanemia as required for both neurological and immune homeostasis.",
author = "Simon Klaessens and Vincent Stroobant and Delia Hoffmann and Mads Gyrd-Hansen and Luc Pilotte and Nathalie Vigneron and {De Plaen}, Etienne and {Van den Eynde}, {Benoit J}",
year = "2021",
doi = "10.1073/pnas.2022447118",
language = "English",
volume = "118",
pages = "e2022447118",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "The National Academy of Sciences of the United States of America",
number = "23",

}

RIS

TY - JOUR

T1 - Tryptophanemia is controlled by a tryptophan-sensing mechanism ubiquitinating tryptophan 2,3-dioxygenase

AU - Klaessens, Simon

AU - Stroobant, Vincent

AU - Hoffmann, Delia

AU - Gyrd-Hansen, Mads

AU - Pilotte, Luc

AU - Vigneron, Nathalie

AU - De Plaen, Etienne

AU - Van den Eynde, Benoit J

PY - 2021

Y1 - 2021

N2 - Maintaining stable tryptophan levels is required to control neuronal and immune activity. We report that tryptophan homeostasis is largely controlled by the stability of tryptophan 2,3-dioxygenase (TDO), the hepatic enzyme responsible for tryptophan catabolism. High tryptophan levels stabilize the active tetrameric conformation of TDO through binding noncatalytic exosites, resulting in rapid catabolism of tryptophan. In low tryptophan, the lack of tryptophan binding in the exosites destabilizes the tetramer into inactive monomers and dimers and unmasks a four-amino acid degron that triggers TDO polyubiquitination by SKP1-CUL1-F-box complexes, resulting in proteasome-mediated degradation of TDO and rapid interruption of tryptophan catabolism. The nonmetabolizable analog alpha-methyl-tryptophan stabilizes tetrameric TDO and thereby stably reduces tryptophanemia. Our results uncover a mechanism allowing a rapid adaptation of tryptophan catabolism to ensure quick degradation of excess tryptophan while preventing further catabolism below physiological levels. This ensures a tight control of tryptophanemia as required for both neurological and immune homeostasis.

AB - Maintaining stable tryptophan levels is required to control neuronal and immune activity. We report that tryptophan homeostasis is largely controlled by the stability of tryptophan 2,3-dioxygenase (TDO), the hepatic enzyme responsible for tryptophan catabolism. High tryptophan levels stabilize the active tetrameric conformation of TDO through binding noncatalytic exosites, resulting in rapid catabolism of tryptophan. In low tryptophan, the lack of tryptophan binding in the exosites destabilizes the tetramer into inactive monomers and dimers and unmasks a four-amino acid degron that triggers TDO polyubiquitination by SKP1-CUL1-F-box complexes, resulting in proteasome-mediated degradation of TDO and rapid interruption of tryptophan catabolism. The nonmetabolizable analog alpha-methyl-tryptophan stabilizes tetrameric TDO and thereby stably reduces tryptophanemia. Our results uncover a mechanism allowing a rapid adaptation of tryptophan catabolism to ensure quick degradation of excess tryptophan while preventing further catabolism below physiological levels. This ensures a tight control of tryptophanemia as required for both neurological and immune homeostasis.

U2 - 10.1073/pnas.2022447118

DO - 10.1073/pnas.2022447118

M3 - Journal article

C2 - 34074763

VL - 118

SP - e2022447118

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 23

ER -

ID: 280715015