The activating transcription factor, ATF-2, is a target of p38 and JNK that are involved in stress-induced apoptosis. Heterozygous Atf-2 mutant (Atf-2+/−) mice are highly prone to mammary tumors. The apoptosis-regulated gene GADD45α and the breast cancer suppressor gene Maspin, both of which are known to be p53 target genes, are downregulated in the mammary tumors arisen in Atf-2+/− mice. Here, we have analysed how ATF-2 controls the transcription of GADD45α and Maspin. ATF-2 and p53 independently activate the GADD45α transcription. ATF-2 does not directly bind to the GADD45α promoter; instead, it is recruited via Oct-1 and NF-I. ATF-2 simultaneously binds to Oct-1, NF-I and breast cancer suppressor BRCA1 to activate transcription. With regard to Maspin, ATF-2 and p53 directly bind to different sites in the Maspin promoter to independently activate its transcription. Consistent with the observation that ATF-2 and p53 independently activate the transcription of Maspin and GADD45α is that the loss of one copy of p53 shortened the period required for mammary tumor development in Atf-2+/− mice. These studies suggest the functional link between the ATF-2 and the two tumor suppressors BRCA1 and p53.

•Trim27-deficient mice are susceptible to streptozotocin-induced diabetes.•Infiltration of T cells is enhanced in Trim27-deficient islets.•Beta-cell mass was decreased in Trim27-deficient islets.•Trim27-deficient mice are not susceptible to dextran sodium sulphate-induced colitis.Tumor necrosis factor α (TNF-α) plays an important role in cell proliferation and apoptosis, and defects in TNF-α-induced apoptosis are associated with various diseases. TRIM27 is a tripartite motif (TRIM) protein containing RING finger, B-box, and coiled-coil domains. We recently reported that TRIM27 positively regulates TNF-α-induced apoptosis through deubiquitination of receptor-interacting protein 1 (RIP1). Multiple studies have suggested a link between TNF-α pathway and various diseases, such as diabetes and colitis. Here, we report that Trim27-deficient mice were susceptible to streptozotocin (STZ)-induced diabetes, a mouse model of diabetes. Infiltration of T cells and cleaved caspase-3 signals were enhanced, and β-cell mass was decreased in Trim27-deficient islets compared to wild-type islets. On the other hand, Trim27-mutation did not affect the dextran sodium sulphate (DSS)-induced colitis. These data support the idea that the TRIM27 mutation is responsible for the development of certain types of diseases.