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Ubiquitin mediated proteolysis

Core of basic research: Deciphers the molecular mechanism by which ubiquitination modification (covalent linkage of ubiquitin molecules to target proteins) regulates protein degradation or function, one of the core protein regulatory pathways in cells. The ubiquitination process is catalyzed by a three-enzyme cascade: E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin ligase). E1 activates ubiquitin and transfers it to E2; E3 recognizes target proteins and mediates the transfer of ubiquitin from E2 to the target protein, forming monoubiquitination or polyubiquitination modifications. Proteins with K48-linked polyubiquitination are degraded by the proteasome; monoubiquitination or other types of linked ubiquitination regulate protein localization, interaction, or enzymatic activity. Research focuses include the substrate recognition specificity of E3 ligases, the reversible regulation of ubiquitination modification (action of deubiquitinating enzymes), and the association of the pathway with cell cycle, signal transduction (e.g., NF-κB pathway), and tumors (E3 ligase mutations).
Core key proteins: Ubiquitin, E1 ubiquitin-activating enzyme (UBE1), E2 ubiquitin-conjugating enzymes (UBE2 family), E3 ubiquitin ligases (RING-type: MDM2, SCF complex; HECT-type: E6AP; RBR-type: Parkin), deubiquitinating enzymes (DUB family: USP, UCH, OTU subfamilies), proteasome (degrades polyubiquitinated proteins), target proteins (cyclins, transcription factors, oncoproteins, etc.), SCF complex (subunits Skp1, Cullin1, F-box protein).

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