Tandem Orthogonal Chemically Induced Dimerization

ChemBioChem ◽  
2013 ◽  
Vol 14 (13) ◽  
pp. 1525-1527 ◽  
Author(s):  
Stephanie Voss ◽  
Yao-Wen Wu
Keyword(s):  
Chemically Induced ◽  
Chemically Induced Dimerization

A DNA-Mediated Chemically Induced Dimerization (D-CID) Nanodevice for Nongenetic Receptor Engineering To Control Cell Behavior

2018 ◽  
Vol 130 (32) ◽  
pp. 10383-10387 ◽  
Author(s):  
Hao Li ◽  
Miao Wang ◽  
Tianhui Shi ◽  
Sihui Yang ◽  
Jinghui Zhang ◽  
...  
Keyword(s):  
Control Cell ◽  
Cell Behavior ◽  
Chemically Induced ◽  
Chemically Induced Dimerization

A DNA-Mediated Chemically Induced Dimerization (D-CID) Nanodevice for Nongenetic Receptor Engineering To Control Cell Behavior

2018 ◽  
Vol 57 (32) ◽  
pp. 10226-10230 ◽  
Author(s):  
Hao Li ◽  
Miao Wang ◽  
Tianhui Shi ◽  
Sihui Yang ◽  
Jinghui Zhang ◽  
...  
Keyword(s):  
Control Cell ◽  
Cell Behavior ◽  
Chemically Induced ◽  
Chemically Induced Dimerization

scholarly journals Liquid condensation drives telomere clustering during ALT

2019 ◽  
Author(s):  
Huaiying Zhang ◽  
Michel Liu ◽  
Robert Dilley ◽  
David M. Chenoweth ◽  
Roger A. Greenberg ◽  
...  
Keyword(s):  
Dna Repair ◽  
Chemical Composition ◽  
Cancer Cells ◽  
Material Properties ◽  
General Framework ◽  
Cellular Functions ◽  
Telomere Elongation ◽  
Alternative Lengthening ◽  
Chemically Induced ◽  
Chemically Induced Dimerization

AbstractTelomerase-free cancer cells employ a recombination-based alternative lengthening of telomeres (ALT) pathway that depends on ALT-associated promyelocytic leukemia (PML) nuclear bodies (APBs), whose function is unclear. We find that APBs behave as liquid condensates, suggesting two potential mechanisms to promote telomere elongation: condensation to enrich DNA repair factors for telomere synthesis and coalescence to cluster telomeres to provide repair templates. Using chemically-induced dimerization, we show that telomere sumoylation nucleates APB condensation via SUMO-SIM (SUMO interaction motif) interactions and clusters telomeres. The induced APBs lack DNA repair factors, indicating that these factors are clients recruited to the APB scaffold rather than components that drive condensation. Telomere clustering, however, relies only on liquid properties of the condensate, as an alternative condensation chemistry also induces clustering. Our results demonstrate how the material properties and chemical composition of APBs independently contribute to ALT, suggesting a general framework for how liquid condensates promote cellular functions.

Pharmacologically regulated Fas-mediated death of adoptively transferred T cells in a nonhuman primate model

Blood ◽  
2004 ◽  
Vol 103 (4) ◽  
pp. 1261-1269 ◽  
Author(s):  
Carolina Berger ◽  
C. Anthony Blau ◽  
Meei-Li Huang ◽  
John D. Iuliucci ◽  
David C. Dalgarno ◽  
...  
Keyword(s):  
T Cells ◽  
Transgene Expression ◽  
Macaca Nemestrina ◽  
Nonhuman Primate Model ◽  
Primate Model ◽  
Enhanced Sensitivity ◽  
Chemically Induced ◽  
Chemically Induced Dimerization

Abstract Conditional suicide genes derived from pathogens have been developed to confer drug sensitivity and enhance safety of cell therapy, but this approach is limited by immune responses to the transgene product. We examined a strategy to regulate survival of transferred cells based on induction of apoptosis through oligomerization of a modified human Fas receptor by a bivalent drug (AP1903). Three macaques (Macaca nemestrina) received autologous T cells retrovirally engineered to express a Fas suicide-construct (LV'VFas). High levels of transduced cells were present in blood following cell transfer, but LV'VFas+ cells declined rapidly after AP1903 administration. A small fraction of LV'VFas+ cells resisted elimination by AP1903, in part due to insufficient levels of transgene expression in resting T cells, because reactivation of these cells in vitro enhanced sensitivity to AP1903. An immune response to the transgene product was observed, but epitope mapping indicated the response was directed to discrete components of human LV'VFas that were variant with the corresponding macaque sequences. These data demonstrate that chemically induced dimerization can be used to regulate survival of adoptively transferred T cells in vivo.

scholarly journals Interaction of INPP5E with ARL13B is essential for its ciliary membrane retention but dispensable for its ciliary entry

Biology Open ◽  
2020 ◽  
pp. bio.057653
Author(s):  
Hantian Qiu ◽  
Sayaka Fujisawa ◽  
Shohei Nozaki ◽  
Yohei Katoh ◽  
Kazuhisa Nakayama
Keyword(s):  
Plasma Membrane ◽  
Steady State ◽  
Small Gtpase ◽  
Membrane Localization ◽  
Wild Type ◽  
Ciliary Membrane ◽  
Chemically Induced ◽  
Chemically Induced Dimerization

Compositions of proteins and lipids within cilia and on the ciliary membrane are maintained to be distinct from those of the cytoplasm and plasma membrane, respectively, by the presence of the ciliary gate. INPP5E is a phosphoinositide 5-phosphatase that is localized on the ciliary membrane by anchorage via its C-terminal prenyl moiety. In addition, the ciliary membrane localization of INPP5E is determined by the small GTPase ARL13B. However, it remained unclear as to how ARL13B participates in the localization of INPP5E. We here show that wild-type INPP5E, INPP5E(WT), in ARL13B-knockout cells and an INPP5E mutant defective in ARL13B binding, INPP5E(ΔCTS), in control cells were unable to show steady-state localization on the ciliary membrane. However, not only INPP5E(WT) but also INPP5E(ΔCTS) was able to rescue the abnormal localization of ciliary proteins in INPP5E-knockout cells. Analysis using the chemically induced dimerization system demonstrated that INPP5E(WT) in ARL13B-knockout cells and INPP5E(ΔCTS) in control cells were able to enter cilia, but neither was retained on the ciliary membrane due to the lack of the INPP5E–ARL13B interaction. Thus, our data demonstrate that binding of INPP5E to ARL13B is essential for its steady-state localization on the ciliary membrane but is dispensable for its entry into cilia.

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