Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As a master regulator of the macroautophagy/autophagy-lysosomal pathway, TFEB (transcription factor EB) plays a prominent role in regulating neurodegenerative diseases and cancer. The transcription activity of TFEB is tightly controlled by phosphorylation and dephosphorylation. Phosphorylated S211 (p-S211) of TFEB can be recognized by YWHA/14-3-3 proteins for TFEB cytoplasmic localization. Here, we characterized the interactions between phosphorylated TFEB and YWHA/14-3-3 proteins and determined the structures of YWHA/14-3-3 proteins in complex with a TFEB p-S211-peptide. Although the critical arginine for YWHA/14-3-3 recognition is missing in the N terminus of the TFEB p-S211-peptide, the C-terminal additional hydrophobic residues of the peptide unexpectedly occupy nearly half of the target-binding groove of YWHA/14-3-3 proteins, which compensates for the N-terminal defect and is distinct from the canonical YWHA/14-3-3-binding mode. Mutations of essential residues in the interaction interface between TFEB and YWHA/14-3-3 proteins disrupted their interactions and severely impaired the cytoplasmic localization of TFEB, which altered the expression of TFEB target genes and affected autophagy. Thus, YWHA/14-3-3 proteins recognize phosphorylated TFEB by a noncanonical mode for controlling TFEB cytoplasmic localization and its activity. Abbreviation: ACTB: actin beta; ALP: autophagy-lysosomal pathway; ATP6V1H: ATPase H+ transporting V1 subunit H; bHLH: basic helix-loop-helix; CLEAR: coordinated lysosomal expression and regulation; Co-IP: co-immunoprecipitation; CTSB: cathepsin B; CTSD: cathepsin D; LAMP1: lysosomal associated membrane protein 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MITF: melanocyte inducing transcription factor; NLS: nuclear localization signal; TFEB: transcription factor EB; YWHA/14-3-3: tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein.
 ...
PMID:YWHA/14-3-3 proteins recognize phosphorylated TFEB by a noncanonical mode for controlling TFEB cytoplasmic localization. 3065 8

The impact of the hydropower plants (HPPs) on the aquatic life is expected, but the biochemical markers of ecotoxicity have not been investigated in relation to HPP proximity. The aim of this study was to compare the responses of mollusk Unio tumidus from the small HPP (reservoir (Ku) and downstream of the dam (Kd)) and micro HPP (upstream (Zu) and downstream of the dam (Zd)). In total, 11 indexes (n) from digestive gland, hemocytes (lysosomal integrity), and gonads (alkali-labile phosphates, ALP) were analyzed. The mollusks from the reservoir demonstrate the typical signs of toxic impact: cholinesterase and glutathione depletion, the highest glutathione S-transferase activity, and ratio of extralysosomal cathepsin D compare to all other groups. The specimens from the micro HPP have the highest levels of glutathione (Zd) and lipid peroxidation (Zu) and lesser Cu/Zn-SOD activity (Zu) than other groups. These indications of stressful conditions may derive from the regular oscillations in the water flow regimes at the micro HPP. For both HPPs, the responses of upstream and downstream groups are distinct. The calculated IBR/n (4.17, 3.85, 3.12, and 0.26 for Ku, Kd, Zu, and Zd correspondingly) gives a quantitative basis for the evaluation of environmental impact of HPPs. Graphical abstract .
 ...
PMID:Multi-marker study of the responses of the Unio tumidus from the areas of small and micro hydropower plants at the Dniester River Basin, Ukraine. 3195 29