Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using a bioinformatic approach, we identified a TP53INP1-related gene encoding a protein with 30% identity with tumor protein 53-induced nuclear protein 1 (TP53INP1), which was named TP53INP2. TP53INP1 and TP53INP2 sequences were found in several species ranging from Homo sapiens to Drosophila melanogaster, but orthologues were found neither in earlier eukaryotes nor in prokaryotes. To gain insight into the function of the TP53INP2 protein, we carried out a yeast two-hybrid screening that showed that TP53INP2 binds to the LC3-related proteins GABARAP and GABARAP-like2, and then we demonstrated by coimmunoprecipitation that TP53INP2 interacts with these proteins, as well as with LC3 and with the autophagosome transmembrane protein VMP1. TP53INP2 translocates from the nucleus to the autophagosome structures after activation of autophagy by rapamycin or starvation. Also, we showed that TP53INP2 expression is necessary for autophagosome development because its small interfering RNA-mediated knockdown strongly decreases sensitivity of mammalian cells to autophagy. Finally, we found that interactions between TP53INP2 and LC3 or the LC3-related proteins GABARAP and GABARAP-like2 require autophagy and are modulated by wortmannin as judged by bioluminescence resonance energy transfer assays. We suggest that TP53INP2 is a scaffold protein that recruits LC3 and/or LC3-related proteins to the autophagosome membrane by interacting with the transmembrane protein VMP1. It is concluded that TP53INP2 is a novel gene involved in the autophagy of mammalian cells.
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PMID:The TP53INP2 protein is required for autophagy in mammalian cells. 1905 83

MAP1LC3/LC3 (microtubule-associated protein 1 light chain 3), a mammalian ortholog of yeast Atg8, is a key protein contributing to major steps of autophagy. It has been recognized for a long time that LC3 is abundant in the nucleus despite the fact that it functions primarily in the cytoplasm where the autophagosomes and autolysosomes arise. An important question regarding nuclear LC3 is whether and how it participates in autophagy. In this punctum, we discuss our recent findings about the essential role for nuclear LC3 in starvation-induced autophagy. During nutrient-rich conditions, LC3 is distributed in an acetylated form in both the nucleus and cytoplasm. Nutrient deprivation promotes the redistribution of LC3 from the nucleus to the cytoplasm. This relocation depends on a deacetylation of the protein by the activated nuclear deacetylase SIRT1 and the association of the protein with its nuclear interaction partner TP53INP2/DOR. More importantly, the deacetylation is also required for LC3 to bind with ATG7 for its subsequent lipidation. Therefore, the results implicate the nuclear pool of LC3 as the primary source of membrane-conjugated LC3, and a regulation of deacetylation and nucleocytoplasmic translocation of LC3 in priming starved cells for autophagy induction.
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PMID:Identifying an essential role of nuclear LC3 for autophagy. 2560 54