PROTAC targeted protein degraders: the past is prologue

Nature Reviews Drug Discovery, Journal Year: 2022, Volume and Issue: 21(3), P. 181 - 200

Published: Jan. 18, 2022

Language: Английский

---

Proteolysis-Targeting Chimeras as Therapeutics and Tools for Biological Discovery

Cell, Journal Year: 2020, Volume and Issue: 181(1), P. 102 - 114

Published: Jan. 16, 2020

Language: Английский

---

The role of JAK-STAT signaling pathway and its regulators in the fate of T helper cells

Cell Communication and Signaling, Journal Year: 2017, Volume and Issue: 15(1)

Published: June 21, 2017

The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway plays critical roles in orchestrating immune system, especially cytokine receptors they can modulate the polarization T helper cells. This is regulated by an array regulator proteins, including Suppressors Cytokine Signaling (SOCS), Protein Inhibitors Activated STATs (PIAS) Tyrosine Phosphatases (PTPs) determining initiation, duration termination signaling cascades. Dysregulation JAK-STAT cells may result various disorders. In this review, we represent how generally then Th cell subsets more detail. Finally, introduce novel targeted strategies as promising therapeutic approaches treatment Studies are ongoing for identifying other regulators designing innovative strategies. Therefore, further investigation needed.

Language: Английский

---

Breaking the chains: deubiquitylating enzyme specificity begets function

Nature Reviews Molecular Cell Biology, Journal Year: 2019, Volume and Issue: 20(6), P. 338 - 352

Published: Feb. 7, 2019

Language: Английский

---

The Ubiquitin Code in the Ubiquitin-Proteasome System and Autophagy

Trends in Biochemical Sciences, Journal Year: 2017, Volume and Issue: 42(11), P. 873 - 886

Published: Sept. 23, 2017

Language: Английский

---

The role of ubiquitination in tumorigenesis and targeted drug discovery

Signal Transduction and Targeted Therapy, Journal Year: 2020, Volume and Issue: 5(1)

Published: Feb. 29, 2020

Ubiquitination, an important type of protein posttranslational modification (PTM), plays a crucial role in controlling substrate degradation and subsequently mediates the "quantity" "quality" various proteins, serving to ensure cell homeostasis guarantee life activities. The regulation ubiquitination is multifaceted works not only at transcriptional levels (phosphorylation, acetylation, methylation, etc.) but also level (activators or repressors). When regulatory mechanisms are aberrant, altered biological processes may induce serious human diseases, especially types cancer. In tumorigenesis, involve tumor metabolism, immunological microenvironment (TME), cancer stem (CSC) stemness so on. With regard some key proteins such as RagA, mTOR, PTEN, AKT, c-Myc P53 significantly regulates activity mTORC1, AMPK PTEN-AKT signaling pathways. addition, TLR, RLR STING-dependent pathways modulates TME. Moreover, core regulator triplets (Nanog, Oct4 Sox2) members Wnt Hippo-YAP participates maintenance CSC stemness. Based on components, including proteasome, E3 ligases, E1, E2 deubiquitinases (DUBs), many molecular targeted drugs have been developed combat Among them, small molecule inhibitors targeting bortezomib, carfilzomib, oprozomib ixazomib, achieved tangible success. MLN7243 MLN4924 (targeting E1 enzyme), Leucettamol A CC0651 nutlin MI-219 compounds G5 F6 DUB activity) shown potential preclinical treatment. this review, we summarize latest progress understanding substrates for their special functions metabolism regulation, TME modulation maintenance. therapeutic targets reviewed, effects drugs.

Language: Английский

---

Ubiquitylation at the crossroads of development and disease

Nature Reviews Molecular Cell Biology, Journal Year: 2017, Volume and Issue: 19(1), P. 59 - 70

Published: Sept. 20, 2017

Language: Английский

---

Ubiquitin-like Protein Conjugation: Structures, Chemistry, and Mechanism

Chemical Reviews, Journal Year: 2017, Volume and Issue: 118(3), P. 889 - 918

Published: Feb. 24, 2017

Ubiquitin-like proteins (Ubl's) are conjugated to target or lipids regulate their activity, stability, subcellular localization, macromolecular interactions. Similar ubiquitin, conjugation is achieved through a cascade of activities that catalyzed by E1 activating enzymes, E2 conjugating and E3 ligases. In this review, we will summarize structural mechanistic details enzymes protein cofactors participate in Ubl cascades. Precisely, focus on machinery the SUMO, NEDD8, ATG8, ATG12, URM1, UFM1, FAT10, ISG15 pathways while referring ubiquitin pathway highlight common contrasting themes. We also review various strategies used trap intermediates during activation conjugation.

Language: Английский

---

Mechanism and inhibition of the papain‐like protease, PLpro, of SARS‐CoV‐2

The EMBO Journal, Journal Year: 2020, Volume and Issue: 39(18)

Published: Aug. 26, 2020

Language: Английский

---

Ubiquitin ligases in oncogenic transformation and cancer therapy

Nature reviews. Cancer, Journal Year: 2017, Volume and Issue: 18(2), P. 69 - 88

Published: Dec. 15, 2017

Language: Английский

---