Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.31 (AMP-activated protein kinase)
 13,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peniciketal A (Pe-A), a spiroketal compound, is isolated from the saline soil-derived fungus Penicillium raistrickii. However, the underlying molecular mechanistic basis for the effects of Pe-A on leukemia is poorly understood. Here, we investigated that Pe-A reduced cell proliferation in three leukemia cell lines (THP-1, K562 and HL60). Importantly, Pe-A showed little cytotoxicity in primary mouse embryonic fibroblast (MEF) cells in a long-duration treatment. For the mechanistic research, we identified 3449 differentially expressed Pe-A-induced proteins through liquid chromatography-tandem mass spectrometry (LC-MS/MS) with TMT label in THP-1 cells. Results showed that many identified proteins were involved in apoptosis and/or autophagy. Then, we confirmed that Pe-A induced not only apoptosis via the mitochondrial pathway but also cytoprotective autophagy by activating the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway indeed. In addition, Pe-A also arrested the cell cycle at the G0-G1 phase by regulating the expressions of checkpoint protein. Collectively, these results provide new insights into the mechanisms that Pe-A may target autophagy-related or apoptosis-related pathways to suppress the development of human leukemia.
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PMID:Effects of a spiroketal compound Peniciketal A and its molecular mechanisms on growth inhibition in human leukemia. 3066 Apr 75

Hibernation is an energy-saving and adaptive strategy adopted by leech, an important medicinal resource in Asia, to survive low temperature. Reversible protein phosphorylation (RPP) plays a key role in the regulation of mammalian hibernation processes but has never been documented in freshwater invertebrate such as leech. In this study, we detected the effects of hibernation on the proteome and phosphoproteome of the leech Whitmania pigra. A total of 2184 proteins and 2598 sites were quantified. Deep-hibernation resulted in 85 up-regulated and 107 down-regulated proteins and 318 up-regulated and 204 down-regulated phosphosites using a 1.5-fold threshold (P<0.05). Proteins involved in protein digestion and absorption, amino acid metabolism and N-glycan biosynthesis were significantly down-regulated during deep-hibernation. However, proteins involved in maintaining cell structure stability in hibernating animals were up-regulated. Differentially phosphorylated proteins provided the first global picture of a shift in energy metabolism, protein synthesis, cytoprotection and signaling during deep hibernation. Furthermore, AMP-activated protein kinase and protein kinase C play major roles in the regulation of these functional processes. These data significantly improve our understanding of the regulatory mechanisms of leech hibernation processes and provides substantial candidate phosphorylated proteins that could be important for functionally adapt in freshwater animals. SIGNIFICANCE: The leech Whitmania pigra as an important medicinal resource in Asia is an excellent model freshwater invertebrate for studies of environmentally-induced hibernation. The present study provides the first quantitative proteomics and phosphoproteomic analysis of leech hibernation using isobaric tag based TMT labeling and high-resolution mass spectrometry. These data significantly improve our understanding of the regulatory mechanisms when ectotherm animals face environmental stress and provides substantial candidate phosphorylated proteins that could be important for functionally adapt in freshwater animals.
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PMID:Proteome and phosphoproteome profiling reveals the regulation mechanism of hibernation in a freshwater leech (Whitmania pigra). 3273 37

Autophagy summarizes evolutionarily conserved, intracellular degradation processes targeting cytoplasmic material for lysosomal degradation. These encompass constitutive processes as well as stress responses, which are often found dysregulated in diseases. Autophagy pathways help in the clearance of damaged organelles, protein aggregates and macromolecules, mediating their recycling and maintaining cellular homeostasis. Protein-protein interaction networks contribute to autophagosome biogenesis, substrate loading, vesicular trafficking and fusion, protein translocations across membranes and degradation in lysosomes. Hypothesis-free proteomic approaches tremendously helped in the functional characterization of protein-protein interactions to uncover molecular mechanisms regulating autophagy. In this review, we elaborate on the importance of understanding protein-protein-interactions of varying affinities and on the strengths of mass spectrometry-based proteomic approaches to study these, generating new mechanistic insights into autophagy regulation. We discuss in detail affinity purification approaches and recent developments in proximity labeling coupled to mass spectrometry, which uncovered molecular principles of autophagy mechanisms. Abbreviations: AMPK: AMP-activated protein kinase; AP-MS: affinity purification-mass spectrometry; APEX2: ascorbate peroxidase-2; ATG: autophagy related; BioID: proximity-dependent biotin identification; ER: endoplasmic reticulum; GFP: green fluorescent protein; iTRAQ: isobaric tag for relative and absolute quantification; MS: mass spectrometry; PCA: protein-fragment complementation assay; PL-MS: proximity labeling-mass spectrometry; PtdIns3P: phosphatidylinositol-3-phosphate; PTM: posttranslational modification; PUP-IT: pupylation-based interaction tagging; RFP: red fluorescent protein; SILAC: stable isotope labeling by amino acids in cell culture; TAP: tandem affinity purification; TMT: tandem mass tag.
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PMID:Protein complexes and neighborhoods driving autophagy. 3318 48