Question

what is a possible mechanism for the disruption of protein degradation pathways?

please be detailed.

Answer 1

PROTEIN DEGRADATION Ubiquitin + ATP 26S Proteasome and ubiquitin to be recycled Proteasome Protein to be degraded Ubiquitinated protein Degraded protein Protein entering into proteasome Ubiquitin-E1 Ubiquitin-E2 Ubiquitin-E3 Ub Protein Protein Ubiquitination by Ubiquitin Ligases Targeting to the Proteosome Proteosome Peptides

PROTEIN DEGRADATION Ubiquitination involves 3 main steps Activation (ubiquitin-activating enzymes (E1s) Conjugation (ubiquitin-conjugating enzymes(E2s) Ligation (ubiquitin ligases (E3s) Activation Conjugation Ligation UD Ly548 Degradation UD E1 E1 E3 (Ubl. Substrate Ub U D E1 Substrate ATP AMP-PP E2 UD Proteasome Substrate ATP ADPP Peptides UD Ub Deubiquitination Ub Lys11 UDU Inhibiting deubiquitinases promotes degradation of oncoproteins Ubiquitin-dependent destruction of cyclin is critical to cell-cycle regulation * MDM2 targets p53 for ubiquitination and proteasomal degradation thus keeping its level appropriate for normal cell condition.

PROTEIN DEGRADATION PATHWAYS Cytosolic ATP dependent pathway (Ubiquitin proteosome pathway) Lysosomal pathway 26S Proteosome involved 80 to 90% degradation Most intracellular proteins • Regulatory Role * Antigen processing Lysosome is involved 10 to 20% degradation • Extracellularproteins Mitochondrial proteolytic system cytoplasmic proteins endosome- lysosome system Lysosome! endosome con Mitochondria Ubiquitin- proteasome system cooperatio Autophagosome ER proteins nuclear proteins proteins Nucleus