TP53 stimulates expression of SESN1,2,3 genes

Sestrins (SESN) are a small family of stress-sensitive gene that are conserved across several species. Mammals express three different SESN family members characterized as SESN1-3. Sestrin genes, SESN1, SESN2 and SESN3, are upregulated in response to TP53-mediated transcriptional regulation. SESN1 and SESN2 were classified as members of the growth arrest and DNA damage (GADD) gene family that can regulate cell growth and viability under different cellular pressures. In particular, p53 negatively modulates the mTOR pahtway via SESN1 and SESN2 upregulation (Feng 2010). SESN3 was identified shortly after SESN2 through in silico analysis and was found to be a target of the forkhead transcription factor (FOXO) family. A specific TP53 binding site on the human SESN3 promoter has not been identified yet, but was found in the rat ortholog (Velasco-Miguel et al. 1999, Budanov et al. 2002, Brynczka et al. 2007).

Sestrins（SESN）是一组在多种物种中得以保守的小型应激敏感基因家族。哺乳动物中表达三种不同的SESN家族成员，分别被标识为SESN1-3。Sestrin基因，包括SESN1、SESN2和SESN3，在受到TP53介导的转录调控后呈现上调。SESN1和SESN2被归类为生长抑制和DNA损伤（GADD）基因家族的成员，能够在不同的细胞压力下调节细胞生长和存活。特别是，p53通过上调SESN1和SESN2，负向调节mTOR通路（Feng 2010）。SESN3在SESN2之后不久通过计算机模拟分析被识别，并被发现是forkhead转录因子（FOXO）家族的靶点。在人类SESN3启动子上的特定TP53结合位点尚未被发现，但在大鼠同源基因中已被找到（Velasco-Miguel等1999年，Budanov等2002年，Brynczka等2007年）。