Oncogenic EML4-ALK assemblies suppress growth factor perception and modulate drug tolerance DOI Creative Commons
David Gonzalez-Martinez, L. E. Roth, Thomas R. Mumford

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Ноя. 2, 2024

Abstract Drug resistance remains a challenge for targeted therapy of cancers driven by EML4-ALK and related fusion oncogenes. forms cytoplasmic protein condensates, which result from networks interactions between oncogene adapter multimers. While these assemblies are associated with oncogenic signaling, their role in drug response is unclear. Here, we use optogenetics live-cell imaging to find that suppress transmembrane receptor tyrosine kinase (RTK) signaling sequestering RTK proteins including GRB2 SOS1. Furthermore, ALK inhibition, while suppressing simultaneously releases the sequestered adapters thereby resensitizes signaling. Resensitized RTKs promote rapid pulsatile ERK reactivation originates paracrine ligands shed dying cells. Reactivated promotes cell survival, can be counteracted combination therapies block Our results identify regulatory uncover mechanism tolerance therapies.

Язык: Английский

A temperature-inducible protein module for control of mammalian cell fate DOI
William Benman, Zikang Huang, Pavan Iyengar

и другие.

Nature Methods, Год журнала: 2025, Номер unknown

Опубликована: Янв. 23, 2025

Язык: Английский

Процитировано

1
Rapid Optogenetic Clustering in the Cytoplasm with BcLOVclust DOI
Zikang Huang, William Benman, Liang Dong

и другие.

Journal of Molecular Biology, Год журнала: 2024, Номер 436(3), С. 168452 - 168452

Опубликована: Янв. 21, 2024

Язык: Английский

Процитировано

7
A temperature-inducible protein module for control of mammalian cell fate DOI Creative Commons
William Benman,

Zikang Huang,

Pavan Iyengar

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 19, 2024

Abstract Inducible protein switches allow on-demand control of proteins in response to inputs including chemicals or light. However, these either cannot be controlled with precision space and time applied optically dense settings, limiting their application tissues organisms. Here we introduce a module whose active state can reversibly toggled small change temperature, stimulus that is both penetrant dynamic. This protein, called Melt ( Me mbrane localization through temperature), exists as monomer the cytoplasm at elevated temperatures but oligomerizes translocates plasma membrane when temperature lowered. The original variant switched states between 28-32°C, changes could observed within minutes change. was highly modular, permitting thermal over diverse processes signaling, proteolysis, nuclear shuttling, cytoskeletal rearrangements, cell death, all straightforward end-to-end fusions. also tunable, giving rise library variants switch point ranging from 30-40°C. higher points allowed molecular circuits 37°C-41°C, well-tolerated range for mammalian cells. Finally, permitted death mouse model human cancer, demonstrating its potential use animals. Thus represents versatile thermogenetic straightforward, non-invasive, spatiotemporally-defined cells broad biotechnology biomedicine.

Язык: Английский

Процитировано

4
Correlative light and electron microscopy imaging of proteinaceous deposits in cell cultures and brain tissues DOI Creative Commons
Peizhou Jiang, Dennis W. Dickson

Acta Neuropathologica Communications, Год журнала: 2025, Номер 13(1)

Опубликована: Март 8, 2025

Язык: Английский

Процитировано

0
Pulsatory response of the BcLOV4 photoreceptor through intramolecular feed-forward regulation DOI Creative Commons
Zikang Huang, Malvin Forson, William Benman

и другие.

Опубликована: Апрель 14, 2025

Abstract Biomolecular networks can dynamically encode information, generating time-varying patterns of activity in response to an input. Here we find that dynamic encoding also be performed by individual proteins. BcLOV4 is optogenetic protein uniquely displays pulsatory activation a step input light, and dynamics shaped both light temperature. However, how the generates this step-to-pulse not understood. combined live cell imaging simulations pulse results from intramolecular incoherent feedforward loop (IFFL) implemented competitive interactions between domains separately respond or We identified these light- temperature-sensitive regions found they implement IFFL competitively caging region. Structural sequence analysis revealed temperature-responsive which allowed experimental tuning suggested has occurred throughout evolution. These findings enabled generation more thermostable tools modular thermosensitive domain endowed thermogenetic control over unrelated Our uncover principles combinatorial signal processing proteins will fuel development sophisticated compact synthetic systems. One-Sentence Summary Individual information through their component domains, revealing for complex natural engineered

Язык: Английский

Процитировано

0
Optogenetic control of condensates: principles and applications DOI
Zikang Huang, Lukasz J. Bugaj

Journal of Molecular Biology, Год журнала: 2024, Номер unknown, С. 168835 - 168835

Опубликована: Окт. 1, 2024

Язык: Английский

Процитировано

1
Development of a Dual Reporter System to Simultaneously Visualize Ca2+ Signals and AMPK Activity DOI Creative Commons
Yusuf C. Erdoğan, Johannes Pilic, Benjamin Gottschalk

и другие.

ACS Sensors, Год журнала: 2024, Номер 9(9), С. 4680 - 4689

Опубликована: Авг. 21, 2024

In this study, we introduce a new separation of phases-based activity reporter kinase (SPARK) for AMP-activated (AMPK), named AMPK-SPARK, which reports the AMPK activation by forming bright fluorescent clusters. Furthermore, dual system, GCaMP-AMPK-SPARK, incorporating single-fluorescent protein (FP)-based Ca

Язык: Английский

Процитировано

0
Oncogenic EML4-ALK assemblies suppress growth factor perception and modulate drug tolerance DOI Creative Commons
David Gonzalez-Martinez, L. E. Roth, Thomas R. Mumford

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Ноя. 2, 2024

Abstract Drug resistance remains a challenge for targeted therapy of cancers driven by EML4-ALK and related fusion oncogenes. forms cytoplasmic protein condensates, which result from networks interactions between oncogene adapter multimers. While these assemblies are associated with oncogenic signaling, their role in drug response is unclear. Here, we use optogenetics live-cell imaging to find that suppress transmembrane receptor tyrosine kinase (RTK) signaling sequestering RTK proteins including GRB2 SOS1. Furthermore, ALK inhibition, while suppressing simultaneously releases the sequestered adapters thereby resensitizes signaling. Resensitized RTKs promote rapid pulsatile ERK reactivation originates paracrine ligands shed dying cells. Reactivated promotes cell survival, can be counteracted combination therapies block Our results identify regulatory uncover mechanism tolerance therapies.

Язык: Английский

Процитировано

0