Prohibitin is required for transcriptional repression by the WT1-BASP1 complex

E. Toska, J. Shandilya, S. J. Goodfellow, K.F. Medler, S.G.E. Roberts (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    16 Citations (Scopus)

    Abstract

    The Wilms’ tumor-1 protein (WT1) is a transcriptional regulator that can either activate or repress genes controlling cell growth, apoptosis and differentiation. The transcriptional corepressor BASP1 interacts with WT1 and mediates WT1’s transcriptional repression activity. BASP1 is contained within large complexes, suggesting that it works in concert with other factors. Here we report that the transcriptional repressor prohibitin is part of the WT1–BASP1 transcriptional repression complex. Prohibitin interacts with BASP1, colocalizes with BASP1 in the nucleus, and is recruited to the promoter region of WT1 target genes to elicit BASP1-dependent transcriptional repression. We demonstrate that prohibitin and BASP1 cooperate to recruit the chromatin remodeling factor BRG1 to WT1-responsive promoters and that this results in the dissociation of CBP from the promoter region of WT1 target genes. As seen with BASP1, prohibitin can associate with phospholipids. We demonstrate that the recruitment of PIP2 and HDAC1 to WT1 target genes is also dependent on the concerted activity of BASP1 and prohibitin. Our findings provide new insights into the function of prohibitin in transcriptional regulation and uncover a BASP1–prohibitin complex that plays an essential role in the PIP2-dependent recruitment of chromatin remodeling activities to the promoter.
    Original languageEnglish
    Pages (from-to)5100-5108
    Number of pages9
    JournalOncogene
    Volume33
    Issue number43
    DOIs
    Publication statusPublished - 23 Oct 2014

    Fingerprint

    Wilms Tumor
    Proteins
    Chromatin Assembly and Disassembly
    Genetic Promoter Regions
    Co-Repressor Proteins
    prohibitin
    Phospholipids
    Apoptosis
    Growth
    Genes

    Keywords

    • WT1
    • BASP1
    • prohibitin
    • Transcription

    Cite this

    Toska, E., Shandilya, J., Goodfellow, S. J., Medler, K. F., & Roberts, S. G. E. (2014). Prohibitin is required for transcriptional repression by the WT1-BASP1 complex. Oncogene, 33(43), 5100-5108. https://doi.org/10.1038/onc.2013.447
    Toska, E. ; Shandilya, J. ; Goodfellow, S. J. ; Medler, K.F. ; Roberts, S.G.E. / Prohibitin is required for transcriptional repression by the WT1-BASP1 complex. In: Oncogene. 2014 ; Vol. 33, No. 43. pp. 5100-5108.
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    Toska, E, Shandilya, J, Goodfellow, SJ, Medler, KF & Roberts, SGE 2014, 'Prohibitin is required for transcriptional repression by the WT1-BASP1 complex', Oncogene, vol. 33, no. 43, pp. 5100-5108. https://doi.org/10.1038/onc.2013.447

    Prohibitin is required for transcriptional repression by the WT1-BASP1 complex. / Toska, E.; Shandilya, J.; Goodfellow, S. J.; Medler, K.F.; Roberts, S.G.E. (Lead / Corresponding author).

    In: Oncogene, Vol. 33, No. 43, 23.10.2014, p. 5100-5108.

    Research output: Contribution to journalArticle

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    Toska E, Shandilya J, Goodfellow SJ, Medler KF, Roberts SGE. Prohibitin is required for transcriptional repression by the WT1-BASP1 complex. Oncogene. 2014 Oct 23;33(43):5100-5108. https://doi.org/10.1038/onc.2013.447