Proteasome-dependent degradation of Daxx by the viral E1B-55K protein in human adenovirus-infected cells.
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Proteasome-dependent degradation of Daxx by the viral E1B-55K protein in human adenovirus-infected cells. / Schreiner, Sabrina; Wimmer, Peter; Sirma, Hüseyin; Everett, Roger D; Blanchette, Paola; Groitl, Peter; Dobner, Thomas.
in: J VIROL, Jahrgang 84, Nr. 14, 14, 2010, S. 7029-7038.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Proteasome-dependent degradation of Daxx by the viral E1B-55K protein in human adenovirus-infected cells.
AU - Schreiner, Sabrina
AU - Wimmer, Peter
AU - Sirma, Hüseyin
AU - Everett, Roger D
AU - Blanchette, Paola
AU - Groitl, Peter
AU - Dobner, Thomas
PY - 2010
Y1 - 2010
N2 - The death-associated protein Daxx found in PML (promyelocytic leukemia protein) nuclear bodies (PML-NBs) is involved in transcriptional regulation and cellular intrinsic antiviral resistence against incoming viruses. We found that knockdown of Daxx in a nontransformed human hepatocyte cell line using RNA interference (RNAi) techniques results in significantly increased adenoviral (Ad) replication, including enhanced viral mRNA synthesis and viral protein expression. This Daxx restriction imposed upon adenovirus growth is counteracted by early protein E1B-55K (early region 1B 55-kDa protein), a multifunctional regulator of cell-cycle-independent Ad5 replication. The viral protein binds to Daxx and induces its degradation through a proteasome-dependent pathway. We show that this process is independent of Ad E4orf6 (early region 4 open reading frame 6), known to promote the proteasomal degradation of cellular p53, Mre11, DNA ligase IV, and integrin alpha3 in combination with E1B-55K. These results illustrate the importance of the PML-NB-associated factor Daxx in virus growth restriction and suggest that E1B-55K antagonizes innate antiviral activities of Daxx and PML-NBs to stimulate viral replication at a posttranslational level.
AB - The death-associated protein Daxx found in PML (promyelocytic leukemia protein) nuclear bodies (PML-NBs) is involved in transcriptional regulation and cellular intrinsic antiviral resistence against incoming viruses. We found that knockdown of Daxx in a nontransformed human hepatocyte cell line using RNA interference (RNAi) techniques results in significantly increased adenoviral (Ad) replication, including enhanced viral mRNA synthesis and viral protein expression. This Daxx restriction imposed upon adenovirus growth is counteracted by early protein E1B-55K (early region 1B 55-kDa protein), a multifunctional regulator of cell-cycle-independent Ad5 replication. The viral protein binds to Daxx and induces its degradation through a proteasome-dependent pathway. We show that this process is independent of Ad E4orf6 (early region 4 open reading frame 6), known to promote the proteasomal degradation of cellular p53, Mre11, DNA ligase IV, and integrin alpha3 in combination with E1B-55K. These results illustrate the importance of the PML-NB-associated factor Daxx in virus growth restriction and suggest that E1B-55K antagonizes innate antiviral activities of Daxx and PML-NBs to stimulate viral replication at a posttranslational level.
M3 - SCORING: Zeitschriftenaufsatz
VL - 84
SP - 7029
EP - 7038
JO - J VIROL
JF - J VIROL
SN - 0022-538X
IS - 14
M1 - 14
ER -
