SPEN is an essential corepressor protein, which probably regulates different key pathways such as the Notch pathway. It is a negative regulator of the Notch pathway via its interaction with RBPSUH, which prevents the association between NOTCH1 and RBPSUH, and therefore suppresses the transactivation activity of Notch signaling. SPEN blocks the differentiation of precursor B-cells into marginal zone B-cells. It probably represses transcription via the recruitment of large complexes containing histone deacetylase proteins. SPEN may bind both to DNA and RNA.
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