Ubiquitination-mediated degradation of SIRT1 by SMURF2 suppresses CRC cell proliferation and tumorigenesis.

The NAD-dependent deacetylase sirtuin 1 (SIRT1), a member of the mammalian sirtuin family, plays a pivotal role in deacetylating histone and nonhistone proteins. Recently, it has been reported that SIRT1 is upregulated in various kinds of tumors and is associated with cell growth and metastasis. However, the factors and molecular mechanism regulating its cellular levels remain to be clarified. Here, we reported that the E3 ubiquitin ligase SMURF2 interacts with SIRT1 and mediates its ubiquitination and degradation. Depletion of SMURF2 leads to SIRT1 upregulation and induces the tumor formation and growth of colorectal cancer in vitro and in vivo. Furthermore, we show a negative correlation between SIRT1 and SMURF2 expression in human colorectal cancer. Thus, we propose a novel mechanism of colorectal tumorigenesis via SIRT1 regulation by SMURF2, which could potentially give rise to a new strategy for the treatment of colorectal cancer.

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