Results 51 to 60 of about 419,478 (257)

Targeted degradation of MERTK and other TAM receptor paralogs by heterobifunctional targeted protein degraders

Frontiers in Immunology, 2023
TAM receptors (TYRO3, AXL, and MERTK) comprise a family of homologous receptor tyrosine kinases (RTK) that are expressed across a range of liquid and solid tumors where they contribute to both oncogenic signaling to promote tumor proliferation and ...
Varsha Gadiyar, Gopi Patel, Jesse Chen, Dominico Vigil, Nan Ji, Veronica Campbell, Kirti Sharma, Yatao Shi, Matthew M. Weiss, Raymond B. Birge, Viralkumar Davra   +10 more
doaj   +1 more source

Targeted Protein Degradation by Small Molecules [PDF]

Annual Review of Pharmacology and Toxicology, 2017
Protein homeostasis networks are highly regulated systems responsible for maintaining the health and productivity of cells. Whereas therapeutics have been developed to disrupt protein homeostasis, more recently identified techniques have been used to repurpose homeostatic networks to effect degradation of disease-relevant proteins.
Daniel P, Bondeson, Craig M, Crews
openaire   +2 more sources

Protein pyrophosphorylation by inositol pyrophosphates — detection, function, and regulation

FEBS Letters, EarlyView.
Protein pyrophosphorylation is an unusual signaling mechanism that was discovered two decades ago. It can be driven by inositol pyrophosphate messengers and influences various cellular processes. Herein, we summarize the research progress and challenges of this field, covering pathways found to be regulated by this posttranslational modification as ...
Sarah Lampe, Tanmay Kumar Mohanty, Rashna Bhandari, Dorothea Fiedler   +3 more
wiley   +1 more source

Targeted protein degradation: expanding the toolbox [PDF]

Nature Reviews Drug Discovery, 2019
Proteolysis-targeting chimeras (PROTACs) and related molecules that induce targeted protein degradation by the ubiquitin-proteasome system represent a new therapeutic modality and are the focus of great interest, owing to potential advantages over traditional occupancy-based inhibitors with respect to dosing, side effects, drug resistance and ...
Schapira, M, Calabrese, M, Bullock, A, Crews, C   +3 more
openaire   +2 more sources

Time after time – circadian clocks through the lens of oscillator theory

FEBS Letters, EarlyView.
Oscillator theory bridges physics and circadian biology. Damped oscillators require external drivers, while limit cycles emerge from delayed feedback and nonlinearities. Coupling enables tissue‐level coherence, and entrainment aligns internal clocks with environmental cues.
Marta del Olmo, Carolin Ector, Hanspeter Herzel   +2 more
wiley   +1 more source

Multiple ETS family transcription factors bind mutant p53 via distinct interaction regions

FEBS Letters, EarlyView.
Mutant p53 gain‐of‐function is thought to be mediated by interaction with other transcription factors. We identify multiple ETS transcription factors that can bind mutant p53 and found that this interaction can be promoted by a PXXPP motif. ETS proteins that strongly bound mutant p53 were upregulated in ovarian cancer compared to ETS proteins that ...
Stephanie A. Metcalf, Nicholas F. Downing, Kaitlyn M. Mills, Samuel C. Metcalfe, Alexander E. Kritzer, Lindsey D. Mayo, Peter C. Hollenhorst   +6 more
wiley   +1 more source

The newfound relationship between extrachromosomal DNAs and excised signal circles

FEBS Letters, EarlyView.
Extrachromosomal DNAs (ecDNAs) contribute to the progression of many human cancers. In addition, circular DNA by‐products of V(D)J recombination, excised signal circles (ESCs), have roles in cancer progression but have largely been overlooked. In this Review, we explore the roles of ecDNAs and ESCs in cancer development, and highlight why these ...
Dylan Casey, Zeqian Gao, Joan Boyes
wiley   +1 more source

Mode of action of a DCAF16-recruiting targeted glue that can selectively degrade BRD9

Nature Communications
Molecular glue degraders for therapeutic target proteins are emerging as a strategy in drug discovery. Here, we modify a BRD9 ligand with specific chemical fragments to create degrader compounds that we call Targeted Glues.
Scott J. Hughes, Wojciech J. Stec, Colin T. R. Davies, David McGarry, Alicia Williams, Marta Carrara, Ivan Del Barco Barrantes, Rebecca Harris, Anna Tasegian, Dominic D. G. Owens, Alexander Fawcett, John Hellicar, Aleksandra Azevedo, Gregor P. Meier, Andrew C. Runcie, Liliana Greger, Martin O’Rourke, Ian Churcher, Martin Pass, Giles A. Brown, Alessio Ciulli, Louise K. Modis, Andrea Testa   +22 more
doaj   +1 more source

Conserved structural motifs in PAS, LOV, and CRY proteins regulate circadian rhythms and are therapeutic targets

FEBS Letters, EarlyView.
Cryptochrome and PAS/LOV proteins play intricate roles in circadian clocks where they act as both sensors and mediators of protein–protein interactions. Their ubiquitous presence in signaling networks has positioned them as targets for small‐molecule therapeutics. This review provides a structural introduction to these protein families.
Eric D. Brinckman, Anna E. Lester, Brian D. Zoltowski   +2 more
wiley   +1 more source

Chemical Inducers of Targeted Protein Degradation [PDF]

Journal of Biological Chemistry, 2010
The functions of many cellular proteins have been elucidated by selective gene inactivation and subsequent phenotypic analysis. For example, genetic mutations, gene knock-out generation, and the use of RNA interference to target mRNA for degradation can all result in decreased production of a specific protein, yielding informative cellular phenotypes ...
Kanak, Raina, Craig M, Crews
openaire   +2 more sources