title: The axis of MAPK1/3-XBP1u-FOXO1 controls autophagic dynamics in cancer cells.
abstract: Earlier studies have shown that macroautophagy is not a constitutively activated process, however, the mechanism of activation is not fully understood. Here, we report that autophagy is a dynamic process in cancer cells in response to glucose starvation. In addition, we determined that FOXO1 turnover is involved in the regulation of this dynamic process. X-box binding protein 1u (XBP1u) plays a critical role in FOXO1 degradation by recruiting FOXO1 to the 20S proteasome. Moreover, the phosphorylation of XBP1u by mitogen-activated protein kinases 1 and 3 (MAPK1/3, also known as ERK2/1) on serine residues 61 and 176 was found to be essential for the enhancement of the interaction between XBP1u and FOXO1. Thus, our findings support the hypothesis that the turnover of FOXO1 induced by MAPK1/3 and XBP1u is a critical factor regulating the autophagic process.
authors: Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, China. zhaoying0812@bjmu.edu.cn
authors: Ying
authors: Y
authors: Zhao
authors: Xue
authors: X
authors: Li
authors: Ke
authors: K
authors: Ma
authors: Jing
authors: J
authors: Yang
authors: Jingyi
authors: J
authors: Zhou
authors: Wan
authors: W
authors: Fu
authors: Fuzheng
authors: F
authors: Wei
authors: Lina
authors: L
authors: Wang
authors: Wei-Guo
authors: WG
authors: Zhu
mesh_terms: D001343:Autophagy; D004268:DNA-Binding Proteins / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005973:Glutamine / Q000172:deficiency / Q000378:metabolism; D045325:HCT116 Cells; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology*; D010766:Phosphorylation; D059748:Proteolysis; D000071701:Regulatory Factor X Transcription Factors; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D005973:Glutamine; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: ERK; FOXO1; XBP1u; autophagy; cancer