E6AP promotes the degradation of the PML tumor suppressor

Louria-Hayon, Igal; Alsheich-Bartok, Osnat; Levav-Cohen, Yaara; Silberman, I.; Berger, Michael; Grossman, Tamar; Matentzoglu, Konstantin; Jiang, Yong-Hui; Müller, Stefan; Scheffner, Martin; Haupt, Sue; Haupt, Ygal

E6AP promotes the degradation of the PML tumor suppressor

Dateien

Louria-Hayon_opus-93842.pdfGröße: 450.67 KBDownloads: 201

Datum

2009

Autor:innen

Louria-Hayon, Igal

Alsheich-Bartok, Osnat

Levav-Cohen, Yaara

Silberman, I.

Berger, Michael

Grossman, Tamar

Matentzoglu, Konstantin

Jiang, Yong-Hui

Müller, Stefan

Scheffner, Martin

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Publikationstyp

Zeitschriftenartikel

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Cell death and differentiation. 2009, 16(8), pp. 1156-1166. ISSN 1350-9047. eISSN 1476-5403. Available under: doi: 10.1038/cdd.2009.31

Zusammenfassung

The promyelocytic leukemia (PML) tumor suppressor is essential for the formation of PML nuclear bodies (NBs). PML and PML-NBs have been implicated in the regulation of growth inhibition, senescence and apoptosis. PML is activated in response to stress signals and is downregulated in certain human cancers. However, the factors mediating PML stability are incompletely understood. Here we demonstrate that a catalytically active form of the mammalian E3 ligase E6AP (HPV E6-associated protein) acts to reduce the half-life of the PML protein by promoting its degradation in the proteasome. E6AP mediates the ubiquitination of PML in an in vitro ubiquitination assay. E6AP and PML interact at physiological levels and colocalize in PML-NBs. Importantly, PML protein expression is elevated in multiple organs and cell types from E6AP null mice and in lymphoid cells is associated with increased number and intensity of PML-NBs. This PML elevation is enhanced in response to DNA damage. Our results identify E6AP as an important regulator of PML and PML-NBs.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Zitieren

ISO 690

LOURIA-HAYON, Igal, Osnat ALSHEICH-BARTOK, Yaara LEVAV-COHEN, I. SILBERMAN, Michael BERGER, Tamar GROSSMAN, Konstantin MATENTZOGLU, Yong-Hui JIANG, Stefan MÜLLER, Martin SCHEFFNER, Sue HAUPT, Ygal HAUPT, 2009. E6AP promotes the degradation of the PML tumor suppressor. In: Cell death and differentiation. 2009, 16(8), pp. 1156-1166. ISSN 1350-9047. eISSN 1476-5403. Available under: doi: 10.1038/cdd.2009.31

BibTex

@article{LouriaHayon2009promo-1126,
  year={2009},
  doi={10.1038/cdd.2009.31},
  title={E6AP promotes the degradation of the PML tumor suppressor},
  number={8},
  volume={16},
  issn={1350-9047},
  journal={Cell death and differentiation},
  pages={1156--1166},
  author={Louria-Hayon, Igal and Alsheich-Bartok, Osnat and Levav-Cohen, Yaara and Silberman, I. and Berger, Michael and Grossman, Tamar and Matentzoglu, Konstantin and Jiang, Yong-Hui and Müller, Stefan and Scheffner, Martin and Haupt, Sue and Haupt, Ygal}
}

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