AbstractE74-like ETS transcription factor 5 (ELF5) is involved in a wide spectrum of biological processes, e.g., mammogenesis and tumor progression. We have identified a list of p300-interacting proteins in human breast cancer cells. Among these, ELF5 was found to interact with p300 via acetylation, and the potential acetylation sites were identified as K130, K134, K143, K197, K228, and K245. Furthermore, an ELF5-specific deacetylase, SIRT6, was also identified. Acetylation of ELF5 promoted its

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... ubiquitination and degradation, but was also essential for its antiproliferative effect against breast cancer, as overexpression of wild-type ELF5 and sustained acetylation-mimicking ELF5 mutant could inhibit the expression of its target gene CCND1. Taken together, the results demonstrated a novel regulation of ELF5 as well as shedding light on its important role in modulation of breast cancer progression.