Dynamic acetylation/deacetylation dictates TRIM27 nuclear-cytoplasmic localization for cancer progression [CUT&Tag]

We have identified that the tripartite motif-containing protein 27 (TRIM27), typically known as an E3 ubiquitin ligase, plays dichotomous roles in cancer progression. These roles are determined by its subcellular localization, which is regulated by acetylation and deacetylation at lysine 297 (K297) independently of its ubiquitin ligase activity.

Acetylation by general control non-repressed protein 5 (GCN5) directs TRIM27 to the nucleus, where it inhibits cancer cell invasion and metastasis by modulating the transcription of paired box 6 (PAX6). Conversely, deacetylation by histone deacetylase 4 (HDAC4) results in cytoplasmic localization, promoting cell proliferation and tumor growth. In the nucleus, TRIM27 binds to poly (ADP-ribose) polymerase 1 (PARP1) and negative elongation factors (NELFs), repressing PARP1-mediated mono-ADP-ribosylation of NELFA, thereby preventing the release of RNA polymerase II from transcriptional pausing, and leading to transcriptional repression of PAX6.