SAM68: Signal Transduction and RNA Metabolism in Human Cancer

Figure 2

Transcriptional regulation by SAM68. (a) SAM68 forms a complex with CBP and transcriptional repressor factors (TF), thus negatively regulating CBP targets transcription [37]. (b) The PIAS1 complex SUMOylates SAM68, which interacts with a histone deacetylase (HDAC) and represses CCDN1 transcription [23]. (c) SAM68 directly interacts with the androgen receptor (AR) and binds to androgen-responsive elements (AREs) leading to AR targets activation (i.e., PSA gene) [38]. (d) SAM68 depletion in breast cancer cells leads to activation of FOXO factors thus inhibiting cell proliferation and tumourigenicity through the upregulation of cyclin-dependent kinase inhibitors p21 (Cip1) and p27 (Kip1) [39]. (e) SAM68 binds the CD25 promoter and facilitates p65 recruitment, thus contributing to NF-κB regulation of gene expression [40].

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