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A novel mouse model for inhibition of DOHH mediated hypusine modification reveals crucial function for embryonic development, proliferation and oncogenic transformation

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A novel mouse model for inhibition of DOHH mediated hypusine modification reveals crucial function for embryonic development, proliferation and oncogenic transformation. / Sievert, Henning; Pällmann, Nora; Miller, Katharine K; Hermans-Borgmeyer, Irmgard; Venz, Simone; Sendoel, Ataman; Preukschas, Michael; Schweizer, Michaela; Böttcher, Steffen; Janiesch, P Christoph; Streichert, Thomas; Walther, Reinhard; Hengartner, Michael O; Manz, Markus G; Brümmendorf, Tim H; Bokemeyer, Carsten; Balabanov, Melanie; Hauber, Joachim; Duncan, Kent E; Balabanov, Stefan.

in: DIS MODEL MECH, 15.05.2014.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Sievert, H, Pällmann, N, Miller, KK, Hermans-Borgmeyer, I, Venz, S, Sendoel, A, Preukschas, M, Schweizer, M, Böttcher, S, Janiesch, PC, Streichert, T, Walther, R, Hengartner, MO, Manz, MG, Brümmendorf, TH, Bokemeyer, C, Balabanov, M, Hauber, J, Duncan, KE & Balabanov, S 2014, 'A novel mouse model for inhibition of DOHH mediated hypusine modification reveals crucial function for embryonic development, proliferation and oncogenic transformation', DIS MODEL MECH. https://doi.org/10.1242/dmm.014449

APA

Sievert, H., Pällmann, N., Miller, K. K., Hermans-Borgmeyer, I., Venz, S., Sendoel, A., Preukschas, M., Schweizer, M., Böttcher, S., Janiesch, P. C., Streichert, T., Walther, R., Hengartner, M. O., Manz, M. G., Brümmendorf, T. H., Bokemeyer, C., Balabanov, M., Hauber, J., Duncan, K. E., & Balabanov, S. (2014). A novel mouse model for inhibition of DOHH mediated hypusine modification reveals crucial function for embryonic development, proliferation and oncogenic transformation. DIS MODEL MECH. https://doi.org/10.1242/dmm.014449

Vancouver

Sievert H, Pällmann N, Miller KK, Hermans-Borgmeyer I, Venz S, Sendoel A et al. A novel mouse model for inhibition of DOHH mediated hypusine modification reveals crucial function for embryonic development, proliferation and oncogenic transformation. DIS MODEL MECH. 2014 Mai 15. https://doi.org/10.1242/dmm.014449

Bibtex

@article{7a10d72270cb47439c4afe534fb3cae4,
title = "A novel mouse model for inhibition of DOHH mediated hypusine modification reveals crucial function for embryonic development, proliferation and oncogenic transformation",
abstract = "The central importance of translational control by posttranslational modification has spurred major interest in regulatory pathways that control translation. One such pathway uniquely adds hypusine to eukaryotic initiation factor 5A (eIF5A), and thereby affects protein synthesis and subsequently cellular proliferation through an unknown mechanism. Using a novel conditional knockout mouse model and a Caenorhabditis elegans knockout model, we found an evolutionarily conserved role for the DOHH-mediated second step of hypusine synthesis in early embryonic development. At the cellular level we observed reduced proliferation and induction of senescence in 3T3 Dohh(-/-) cells as well as reduced capability for malignant transformation. Furthermore, by mass spectrometry we observed that deletion of DOHH results in an unexpected complete loss of hypusine modification. Our results provide new biological insight into the physiological roles of the second step of the hypusination of eIF5A. Moreover, the conditional mouse model presented here provides a powerful tool to manipulate hypusine modification in a temporal and spatial manner, both to analyze how this unique modification normally functions in vivo, as well as how it contributes to different pathological conditions.",
author = "Henning Sievert and Nora P{\"a}llmann and Miller, {Katharine K} and Irmgard Hermans-Borgmeyer and Simone Venz and Ataman Sendoel and Michael Preukschas and Michaela Schweizer and Steffen B{\"o}ttcher and Janiesch, {P Christoph} and Thomas Streichert and Reinhard Walther and Hengartner, {Michael O} and Manz, {Markus G} and Br{\"u}mmendorf, {Tim H} and Carsten Bokemeyer and Melanie Balabanov and Joachim Hauber and Duncan, {Kent E} and Stefan Balabanov",
year = "2014",
month = may,
day = "15",
doi = "10.1242/dmm.014449",
language = "English",
journal = "DIS MODEL MECH",
issn = "1754-8403",
publisher = "Company of Biologists Ltd",

}

RIS

TY - JOUR

T1 - A novel mouse model for inhibition of DOHH mediated hypusine modification reveals crucial function for embryonic development, proliferation and oncogenic transformation

AU - Sievert, Henning

AU - Pällmann, Nora

AU - Miller, Katharine K

AU - Hermans-Borgmeyer, Irmgard

AU - Venz, Simone

AU - Sendoel, Ataman

AU - Preukschas, Michael

AU - Schweizer, Michaela

AU - Böttcher, Steffen

AU - Janiesch, P Christoph

AU - Streichert, Thomas

AU - Walther, Reinhard

AU - Hengartner, Michael O

AU - Manz, Markus G

AU - Brümmendorf, Tim H

AU - Bokemeyer, Carsten

AU - Balabanov, Melanie

AU - Hauber, Joachim

AU - Duncan, Kent E

AU - Balabanov, Stefan

PY - 2014/5/15

Y1 - 2014/5/15

N2 - The central importance of translational control by posttranslational modification has spurred major interest in regulatory pathways that control translation. One such pathway uniquely adds hypusine to eukaryotic initiation factor 5A (eIF5A), and thereby affects protein synthesis and subsequently cellular proliferation through an unknown mechanism. Using a novel conditional knockout mouse model and a Caenorhabditis elegans knockout model, we found an evolutionarily conserved role for the DOHH-mediated second step of hypusine synthesis in early embryonic development. At the cellular level we observed reduced proliferation and induction of senescence in 3T3 Dohh(-/-) cells as well as reduced capability for malignant transformation. Furthermore, by mass spectrometry we observed that deletion of DOHH results in an unexpected complete loss of hypusine modification. Our results provide new biological insight into the physiological roles of the second step of the hypusination of eIF5A. Moreover, the conditional mouse model presented here provides a powerful tool to manipulate hypusine modification in a temporal and spatial manner, both to analyze how this unique modification normally functions in vivo, as well as how it contributes to different pathological conditions.

AB - The central importance of translational control by posttranslational modification has spurred major interest in regulatory pathways that control translation. One such pathway uniquely adds hypusine to eukaryotic initiation factor 5A (eIF5A), and thereby affects protein synthesis and subsequently cellular proliferation through an unknown mechanism. Using a novel conditional knockout mouse model and a Caenorhabditis elegans knockout model, we found an evolutionarily conserved role for the DOHH-mediated second step of hypusine synthesis in early embryonic development. At the cellular level we observed reduced proliferation and induction of senescence in 3T3 Dohh(-/-) cells as well as reduced capability for malignant transformation. Furthermore, by mass spectrometry we observed that deletion of DOHH results in an unexpected complete loss of hypusine modification. Our results provide new biological insight into the physiological roles of the second step of the hypusination of eIF5A. Moreover, the conditional mouse model presented here provides a powerful tool to manipulate hypusine modification in a temporal and spatial manner, both to analyze how this unique modification normally functions in vivo, as well as how it contributes to different pathological conditions.

U2 - 10.1242/dmm.014449

DO - 10.1242/dmm.014449

M3 - SCORING: Journal article

C2 - 24832488

JO - DIS MODEL MECH

JF - DIS MODEL MECH

SN - 1754-8403

ER -