TRIP12 promotes small-molecule-induced degradation through K29/K48-branched ubiquitin chains

• Published in: Molecular cell Vol. 81; no. 7; pp. 1411 - 1424.e7
• Main Authors: Kaiho-Soma, Ai, Akizuki, Yoshino, Igarashi, Katsuhide, Endo, Akinori, Shoda, Takuji, Kawase, Yasuko, Demizu, Yosuke, Naito, Mikihiko, Saeki, Yasushi, Tanaka, Keiji, Ohtake, Fumiaki
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2021
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; apoptosis; cancer; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; cullin-RING ligase; epigenetics; HCT116 Cells; HEK293 Cells; Humans; Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Polyubiquitin - genetics; Polyubiquitin - metabolism; protein degradation; Proteolysis; Receptors, Cytokine - genetics; Receptors, Cytokine - metabolism; Receptors, Retinoic Acid - genetics; Receptors, Retinoic Acid - metabolism; targeted protein degradation; therapeutics; Transcription Factors - genetics; Transcription Factors - metabolism; ubiquitin; ubiquitin-protein ligase; Ubiquitin-Protein Ligases - genetics; Ubiquitin-Protein Ligases - metabolism; ubROTAC; ubROTAC; cullin-RING ligase; targeted protein degradation; apoptosis; cancer; epigenetics; ubiquitin

Targeted protein degradation is an emerging therapeutic paradigm. Small-molecule degraders such as proteolysis-targeting chimeras (PROTACs) induce the degradation of neo-substrates by hijacking E3 ubiquitin ligases. Although ubiquitylation of endogenous substrates has been extensively studied, the m...