1
Yip et al
- E2/E3 enzyme for protein quality control (targets orphan proteins, ribosomes)
- Client selection uses ubiquitin binding + cofactor (NAP1L1)
- Initial ubiquitin on client → ↑ UBE2O binding → multi-mono-ubiquitylation (feed-forward)
- NAP1L1 acts as adaptor to recruit specific clients
- Has SH3-like ubiquitin-binding domain for client recognition
- Autoinhibited → activated upon client/ubiquitin binding (multivalency drives selection)
2
Collins
- Degrades polyubiquitylated proteins (ATP-dependent)
- Steps: recognition → deubiquitylation → unfolding → translocation → degradation
- Needs unstructured region to initiate degradation
- Processive: fully degrades once committed
- Regulated (DUBs, ubiquitin chains, phosphorylation) to ensure specificity + control
3
Fomicheva
- Genome-wide CRISPR screen → finds regulators of cell density–controlled growth
- Key hit: TRAF3 (normally inhibits NF-κB signaling)
- Loss of TRAF3 → activates noncanonical NF-κB
- Activates innate immune signaling → continued proliferation at high density
- Bypasses normal controls (independent of YAP/TAZ + CDK inhibitors)
- Mechanism: prevents entry into quiescence
4
Ignolia
- Technique: sequences ribosome-protected mRNA fragments → shows where ribosomes sit on transcripts
- Provides codon-level resolution of translation
- Measures:
- Translation efficiency of genes
- Ribosome density along mRNAs
- Start/stop sites, pausing, frameshifting
- Allows genome-wide view of protein synthesis
- Reveals new regulatory features: upstream ORFs, alternative initiation, translational control