Targeted protein degradation: from small molecules to complex organelles—a Keystone Symposia report

Cable, Jennifer; Weber‐Ban, Eilika; Clausen, Tim; Walters, Kylie J.; Sharon, Michal; Finley, Daniel; Gu, Yangnan; Hanna, John; Feng, Yue; Martens, Sascha; Simonsen, Anne; Hansen, Malene; Zhang, Hong; Goodwin, Jonathan M.; Reggio, Alessio; Chang, Chunmei; Ge, Liang; Schulman, Brenda A.; Deshaies, Raymond J.; Đikić, Ivan; Harper, J. Wade; Wertz, Ingrid E.; Thomä, Nicolas H.; Słabicki, Mikołaj; Frydman, Judith; Jakob, Ursula; David, Della; Bennett, Eric J.; Bertozzi, Carolyn R.; Sardana, Richa; Eapen, Vinay V.; Carra, Serena

doi:10.1111/nyas.14745

Cited by 6 publications

(6 citation statements)

References 143 publications

(279 reference statements)

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“…(170)(171)(172)(173)(174)(175) as antimalarial agents (Figure 39a). [60] The design of these complexes is similar to that of the Ru(II) complexes (134,138) and of Rh(III) complexes (135)(136)(137)(139)(140)(141). They also reported the X-ray crystal structure of 174 (Figure 39b).…”

Section: Antimalarial Activity Of 5 D Metal-based Complexessupporting

confidence: 53%

“…[138] These vesicles contain 20S proteasome which degrades certain cytoskeletal proteins of the RBC. [139,140] This degradation alters the stiffness of RBC's membrane, ultimately promoting parasite growth. [141][142] A tripeptide vinyl sulfone (WLW-vs; W = tryptophan; L = leucine) was found to selectively inhibit the β2 site (trypsin-like (TÀ L) site) of 20S proteasome of P. falciparum.…”

Section: Antimalarial Activity Of 3 D Metal-based Complexesmentioning

confidence: 99%

“…Unfortunately, sulfadoxine is becoming inactive against P. falciparum due to increased drug resistance. [178][179][180][181] Recently, Chellan et al has explored the antimalarial potential of Ru(II) and Rh(III) complexes (134)(135)(136)(137)(138)(139)(140)(141) where sulfadoxine derivative was one of the ligands (Figure 30). [60] The sulfadoxine derivatives (L43, L44), and the complexes 134-141 were prepared following the procedures given in Figure 30.…”

Section: Antimalarial Activity Of 4 D Metal-based Complexesmentioning

confidence: 99%

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Transition Metal Complexes as Antimalarial Agents: A Review

et al. 2023

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In antimalarial drug development research, overcoming drug resistance has been a major challenge for researchers. Nowadays, several drugs like chloroquine, mefloquine, sulfadoxine, and artemisinin are used to treat malaria. But increment in drug resistance has pushed researchers to find novel drugs to tackle drug resistance problems. The idea of using transition metal complexes with pharmacophores as ligands/ligand pendants to show enhanced antimalarial activity with a novel mechanism of action has gained significant attention recently. The advantages of metal complexes include tunable chemical/physical properties, redox activity, avoiding resistance factors, etc. Several recent reports have successfully demonstrated that the metal complexation of known organic antimalarial drugs can overcome drug resistance by showing enhanced activities than the parent drugs. This review has discussed the fruitful research works done in the past few years falling into this criterion. Based on transition metal series (3d, 4d, or 5d), the antimalarial metal complexes have been divided into three broad categories (3d, 4d, or 5d metal‐based), and their activities have been compared with the similar control complexes as well as the parent drugs. Furthermore, we have also commented on the potential issues and their possible solution for translating these metal‐based antimalarial complexes into the clinic.

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Section: Antimalarial Activity Of 5 D Metal-based Complexessupporting

confidence: 53%

Section: Antimalarial Activity Of 3 D Metal-based Complexesmentioning

confidence: 99%

Section: Antimalarial Activity Of 4 D Metal-based Complexesmentioning

confidence: 99%

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Transition Metal Complexes as Antimalarial Agents: A Review

et al. 2023

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“…Protein degradation plays fundamental regulatory roles and essential housekeeping functions. [ 47 ] Protein degradation also regulates protein fate in response to specific intrinsic and extrinsic cues to regulate signaling events. Depending on the specific roles of the degraded protein, the consequences of target protein degradation are diverse.…”

Section: Mechanisms Of Arf Degradationmentioning

confidence: 99%

AUXIN RESPONSE FACTOR protein accumulation and function

Jing

Strader

2023

BioEssays

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Auxin is a key regulator of plant developmental processes. Its effects on transcription are mediated by the AUXIN RESPONSE FACTOR (ARF) family of transcription factors. ARFs tightly control specific auxin responses necessary for proper plant growth and development. Recent research has revealed that regulated ARF protein accumulation and ARF nucleo‐cytoplasmic partitioning can determine auxin transcriptional outputs. In this review, we explore these recent findings and consider the potential for regulated ARF accumulation in driving auxin responses in plants.

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“…Autophagy is a highly conserved degradation pathway that is essential for eukaryotic cell homeostasis and health [1]. Among the various types of autophagy [2], macroautophagy (hereafter autophagy) is the best characterized one.…”

Section: Introductionmentioning

confidence: 99%

Effect of ATG12–ATG5-ATG16L1 autophagy E3-like complex on the ability of LC3/GABARAP proteins to induce vesicle tethering and fusion

Etxaniz

Varela

Lázaro

et al. 2023

Cell. Mol. Life Sci.

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In macroautophagy, the autophagosome (AP) engulfs portions of cytoplasm to allow their lysosomal degradation. AP formation in humans requires the concerted action of the ATG12 and LC3/GABARAP conjugation systems. The ATG12–ATG5-ATG16L1 or E3-like complex (E3 for short) acts as a ubiquitin-like E3 enzyme, promoting LC3/GABARAP proteins anchoring to the AP membrane. Their role in the AP expansion process is still unclear, in part because there are no studies comparing six LC3/GABARAP family member roles under the same conditions, and also because the full human E3 was only recently available. In the present study, the lipidation of six members of the LC3/GABARAP family has been reconstituted in the presence and absence of E3, and the mechanisms by which E3 and LC3/GABARAP proteins participate in vesicle tethering and fusion have been investigated. In the absence of E3, GABARAP and GABARAPL1 showed the highest activities. Differences found within LC3/GABARAP proteins suggest the existence of a lipidation threshold, lower for the GABARAP subfamily, as a requisite for tethering and inter-vesicular lipid mixing. E3 increases and speeds up lipidation and LC3/GABARAP-promoted tethering. However, E3 hampers LC3/GABARAP capacity to induce inter-vesicular lipid mixing or subsequent fusion, presumably through the formation of a rigid scaffold on the vesicle surface. Our results suggest a model of AP expansion in which the growing regions would be areas where the LC3/GABARAP proteins involved should be susceptible to lipidation in the absence of E3, or else a regulatory mechanism would allow vesicle incorporation and phagophore growth when E3 is present.

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Targeted protein degradation: from small molecules to complex organelles—a Keystone Symposia report

Cited by 6 publications

References 143 publications

Transition Metal Complexes as Antimalarial Agents: A Review

Transition Metal Complexes as Antimalarial Agents: A Review

AUXIN RESPONSE FACTOR protein accumulation and function

Effect of ATG12–ATG5-ATG16L1 autophagy E3-like complex on the ability of LC3/GABARAP proteins to induce vesicle tethering and fusion

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