Protein degradation

Protein degradation spans the ubiquitin–proteasome system (UPS) and autophagy–lysosome routes—central hubs for proteostasis and signal resetting. We provide tools for ubiquitin/ligases, p97/VCP, autophagy markers, and PROTAC-oriented readouts from basic regulation to targeted protein degradation (TPD).

Focus areas: E3 substrate recognition & CRL dynamics, ERAD–p97 axis, selective autophagy receptors, rational PROTAC/molecular-glue design

Protein-degradation-related antibodies (curated)

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Hot topics & directions

  • UPS substrate recognition & timing: How phosphorylation/conformation couples to SCF/CRL recruitment.
  • ERAD & the p97/VCP machine: Extraction of misfolded proteins, DUBs, and delivery to the proteasome.
  • Autophagic flux & selective receptors: p62, NDP52, etc.—division of labor vs redundancy in ubiquitinated cargo.
  • PROTACs & targeted degradation: Ternary complex formation, ligandable E3s, and tissue-selective degradation windows.

Related targets

Ubiquitination machinery
UBE1/2/3 enzymes, RING/U-box/HECT ligases, HSP70/90 chaperones
Proteasome & regulation
PSMA/B/C subunits, Rpn11/Rpn13, PA28/11S regulators (context)
Core autophagy machinery
ULK1 complex, PI3KC3-C1, ATG5–ATG12, LC3 conjugation system, TFEB/TFE3
TPD-relevant E3 ligases
CRBN, VHL, IAPs (cIAP1/2), DCAF15/DCAF16 (glue contexts; model-dependent)

Key signaling pathways

  1. Ub → E1 → E2 → E3 → substrate poly-Ub → 26S proteasome
    Canonical chain; linkage type/length steers recognition and fate.
  2. ERAD: Hrd1/Sel1L–gp78–VCP modules
    ER quality control intersects viral evasion—substrate-dependent.
  3. Selective autophagy: Ub–receptor–LC3/LIR axis
    Mitophagy vs aggrephagy share modules but differ in receptor usage.
  4. PROTAC: POI–PROTAC–E3 ternary complex → ubiquitination
    Bindable ≠ degradable—measure kinetics and off-tumor risk.

Tool compounds (research use)

Commonly used for mechanistic studies; follow your lab SOP, compound datasheets, and ethics approvals.

CompoundTargets / pathwaysExperimental notes
MG132Proteasome (reversible tool)Common UPS-dependency probe; cytotoxic—tightly window dose and time.
LactacystinProteasome (irreversible; β-subunit–related)Relatively clean proteasome tool; still cytotoxic—pair controls.
MLN4924 (Pevonedistat)NEDDylation / NAE1CRL-axis intervention; mind cell-cycle context and substrate differences.
ChloroquineLysosomal acidification (autophagic flux block)Often paired with BafA1 to stage flux; mind cardiotoxicity literature.
Bafilomycin A1V-ATPase / lysosomal acidificationBlocks downstream fusion/degradation steps; potent—mind vehicle and nM doses.
3-MethyladeninePI3K class III (autophagy initiation–related)Classic but promiscuous—better for coarse modulation than single-mechanism claims.
CB-5083p97 / VCP ATPaseERAD/stress-granule contexts; watch mitochondrial/cell-death phenotypes.