TY - JOUR TI - Transglutaminase 2 contributes to a TP53-induced autophagy program to prevent oncogenic transformation AU - Yeo, Shi Yun AU - Itahana, Yoko AU - Guo, Alvin Kunyao AU - Han, Rachel AU - Iwamoto, Kozue AU - Nguyen, Hung Thanh AU - Bao, Yi AU - Kleiber, Kai AU - Wu, Ya Jun AU - Bay, Boon Huat AU - Voorhoeve, Mathijs AU - Itahana, Koji A2 - Espinosa, JoaquĆ­n M VL - 5 PY - 2016 DA - 2016/03/09 SP - e07101 C1 - eLife 2016;5:e07101 DO - 10.7554/eLife.07101 UR - https://doi.org/10.7554/eLife.07101 AB - Genetic alterations which impair the function of the TP53 signaling pathway in TP53 wild-type human tumors remain elusive. To identify new components of this pathway, we performed a screen for genes whose loss-of-function debilitated TP53 signaling and enabled oncogenic transformation of human mammary epithelial cells. We identified transglutaminase 2 (TGM2) as a putative tumor suppressor in the TP53 pathway. TGM2 suppressed colony formation in soft agar and tumor formation in a xenograft mouse model. The depletion of growth supplements induced both TGM2 expression and autophagy in a TP53-dependent manner, and TGM2 promoted autophagic flux by enhancing autophagic protein degradation and autolysosome clearance. Reduced expression of both CDKN1A, which regulates the cell cycle downstream of TP53, and TGM2 synergized to promote oncogenic transformation. Our findings suggest that TGM2-mediated autophagy and CDKN1A-mediated cell cycle arrest are two important barriers in the TP53 pathway that prevent oncogenic transformation. KW - TGM2 KW - oncogenic transformation KW - TP53 KW - autophagy KW - CDKN1A JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -