Outfoxing FoxO transcription factors: HTLV-1 Tax oncoprotein inactivates FoxO4 via the ubiquitin-proteasome pathway

Noula Shembade, Edward W. Harhaj

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Evaluation of: Oteiza A, Mechti N. The human T-cell leukemia virus type 1 oncoprotein tax controls forkhead box O4 activity through degradation by the proteasome. J. Virol. 85(13), 6480-6491 (2011). This study examines downstream signaling events of PI3K/AKT in the context of human T cell leukemia virus type 1 (HTLV-1) infection. The authors have demonstrated that the HTLV-1 Tax oncoprotein triggers the ubiquitination and proteasomal degradation of the FoxO4 transcription factor. Phosphorylation by AKT is requisite for Tax-induced FoxO4 degradation since mutation of the AKT phosphorylation sites abrogates FoxO4 degradation. Furthermore, Tax enhances the interaction between FoxO4 and the E3 ubiquitin ligase MDM2 which presumably leads to FoxO4 ubiquitination. Consistently, knockdown of MDM2 with a shRNA plasmid attenuates FoxO4 ubiquitination, revealing an important role for MDM2 in Tax-induced FoxO4 ubiquitination. Finally, Tax represses FoxO4 transcriptional activity in a dose-dependent manner. Taken together, the findings by Oteiza et al. suggest that Tax inactivates the tumor suppressor FoxO4 downstream of PI3K/AKT, which may play a role in HTLV-1-induced oncogenesis.

Original languageEnglish
Pages (from-to)1165-1168
Number of pages4
JournalFuture Virology
Volume6
Issue number10
DOIs
StatePublished - Oct 1 2011

Fingerprint

Deltaretrovirus
Ubiquitination
Oncogene Proteins
Proteasome Endopeptidase Complex
Ubiquitin
Transcription Factors
Phosphatidylinositol 3-Kinases
Phosphorylation
Ubiquitin-Protein Ligases
Virus Diseases
Small Interfering RNA
Carcinogenesis
Plasmids
Mutation
Neoplasms

Keywords

  • AKT
  • FoxO4
  • HTLV-1
  • MDM2
  • proteasome
  • Tax
  • ubiquitination

ASJC Scopus subject areas

  • Virology

Cite this

Outfoxing FoxO transcription factors : HTLV-1 Tax oncoprotein inactivates FoxO4 via the ubiquitin-proteasome pathway. / Shembade, Noula; Harhaj, Edward W.

In: Future Virology, Vol. 6, No. 10, 01.10.2011, p. 1165-1168.

Research output: Contribution to journalArticle

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