mTOR regulates autophagy-associated genes downstream of p73.
The p53 family consists of three transcription factors, p53, p63 and p73 that share domain architecture and sequence identity. The mTOR (mammalian target of rapamycin) kinase responds to growth factors and nutrient levels to regulate cellular growth and autophagy. Whereas p53 acts both upstream and downstream of mTOR, gene signature-based analyses have revealed that p73 is inhibited by mTOR activity. p53 can both activate and repress autophagy levels depending on cellular context. While less is known about p73, recent studies have shown that it induces cellular autophagy and multiple autophagy-associated genes downstream of mTOR. Chromatin immunoprecipitation analyses demonstrate that endogenous p73 binds the regulatory regions of genes such as ATG5, ATG7 and UVRAG. How p73 regulates the expression levels of these genes in response to different cellular stresses remains unknown. Because p53 family members play key roles in tumor suppression, development, aging and neurodegeneration, the context and manner by which these transcription factors regulate autophagy may have implications for a wide range of human diseases.
Rosenbluth
Jennifer M
JM
Department of Biochemistry, Center in Molecular Toxicology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Pietenpol
Jennifer A
JA
D000818:Animals; D001343:Autophagy / Q000235:genetics*; D001483:Base Sequence; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011494:Protein Kinases / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D025521:Tumor Suppressor Proteins; D011494:Protein Kinases; C546842:MTOR protein, human; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases