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p21 Half-Life: Protein Degradation Pathway Comparison
CRL4-Cdt2 CRL4-Cdt2 complex PIP-degron (TD motif, residues 156–160) S phase (chromatin-bound p21) 20–30 minutes Dominant pathway during DNA replication; mutation of T156 extends half-life to >2 hours SCF-Skp2 SCF-Skp2 complex Phospho-T145 recognition G1/S tran
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- CRL4-Cdt2
- CRL4-Cdt2 complex
- PIP-degron (TD motif, residues 156–160)
- S phase (chromatin-bound p21)
- 20–30 minutes
- Dominant pathway during DNA replication; mutation of T156 extends half-life to >2 hours
- SCF-Skp2
- SCF-Skp2 complex
- Phospho-T145 recognition
- G1/S transition (cytoplasmic p21)
- 30–45 minutes
- Activated by growth factor signalling through AKT; accounts for rapid clearance during mitogenic stimulation
- Stabilised (DNA damage)
- E3 ligases inhibited
- Acetylation at K161/163/164 blocks ubiquitination
- G1 arrest (stress response)
- 90–120 minutes
- p53-dependent transcription + post-translational stabilisation; allows p21 accumulation for cell cycle arrest
- Quiescent cells
- Reduced proteasome activity
- Reduced E3 ligase expression
- G0 (non-dividing)
- 60–90 minutes
- Baseline degradation continues but slowed due to low proteasome throughput and lack of replication-coupled degradation