Genetically encoded fluorescent biosensors illuminate kinase signaling in cancer [Cell Biology]

August 21st, 2019 by Wei Lin, Sohum Mehta, Jin Zhang

Protein kinase signaling networks stringently regulate cellular processes, such as proliferation, motility, and cell survival. These networks are also central to the evolution and progression of cancer. Accordingly, genetically encoded fluorescent biosensors capable of directly illuminating the spatiotemporal dynamics of kinase signaling in live cells are being increasingly used to investigate kinase signaling in cancer cells and tumor tissue sections. These biosensors enable visualization of biological processes and events directly in situ, preserving the native biological context and providing detailed insight into their localization and dynamics in cells. Herein, we first review common design strategies for kinase activity biosensors, including signaling targets, biosensor components and fluorescent proteins involved. Subsequently, we discuss applications of biosensors to study the biology and management of cancer. These versatile molecular tools have been deployed to study oncogenic kinase signaling in living cells, image kinase activities in tumors, or decipher the mechanisms of anticancer drugs. We anticipate that the diversity and precision of genetically encoded biosensors will expand their use to further unravel the dysregulation of kinase signaling in cancer and the modes of actions of cancer-targeting drugs.

T(oo)bAd

August 19th, 2019 by Priscille Brodin

Nature Chemical Biology, Published online: 19 August 2019; doi:10.1038/s41589-019-0347-x

An unusual terpene nucleoside, 1-TbAd, made by pathogenic mycobacteria acts as an antacid to block mycobacterial degradation in host cell vacuoles. The antacid activity acts to reduce acidity by neutralizing the pH of these degradative cell organelles.

Stick it to proteins

August 19th, 2019 by Mirella Bucci

Nature Chemical Biology, Published online: 19 August 2019; doi:10.1038/s41589-019-0361-z

Stick it to proteins

Switching on germination

August 19th, 2019 by Caitlin Deane

Nature Chemical Biology, Published online: 19 August 2019; doi:10.1038/s41589-019-0358-7

Switching on germination

<i>Mycobacterium tuberculosis</i> releases an antacid that remodels phagosomes

August 19th, 2019 by Jeffrey Buter

Nature Chemical Biology, Published online: 19 August 2019; doi:10.1038/s41589-019-0336-0

Buter et al. elucidated the biological function of the terpene nucleoside 1-TbAd, which is made abundantly by virulent but not avirulent Mycobacterium tuberculosis strains, and demonstrate that 1-TbAd regulates the pH and function of host macrophage endolysosomes.
  • Posted in Nat Chem Biol, Publications
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Emerging structural insights into glycosyltransferase-mediated synthesis of glycans

August 19th, 2019 by Kelley W. Moremen

Nature Chemical Biology, Published online: 19 August 2019; doi:10.1038/s41589-019-0350-2

Analysis of recent X-ray crystallography data on eukaryotic glycosyltransferases in complex with acceptor and donor substrates reveals structural features that govern substrate specificity and glycosylation site selection.
  • Posted in Nat Chem Biol, Publications
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Lights, enzyme, action!

August 19th, 2019 by Caitlin Deane

Nature Chemical Biology, Published online: 19 August 2019; doi:10.1038/s41589-019-0360-0

Lights, enzyme, action!

Breathing the same air

August 19th, 2019 by Grant Miura

Nature Chemical Biology, Published online: 19 August 2019; doi:10.1038/s41589-019-0359-6

Breathing the same air

Toll-like receptor mediated inflammation requires FASN-dependent MYD88 palmitoylation

August 19th, 2019 by Young-Chan Kim

Nature Chemical Biology, Published online: 19 August 2019; doi:10.1038/s41589-019-0344-0

Inhibition of fatty acid synthase, FASN, blocks innate immune signaling through TLR/MyD88 in neutrophils by blocking palmitoylation of MyD88 by palmitoyltransferase zDHHC6 and improves outcomes in two mouse models of sepsis.
  • Posted in Nat Chem Biol, Publications
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Polar-opposite fates

August 12th, 2019 by Helena R. Ma

Nature Chemical Biology, Published online: 12 August 2019; doi:10.1038/s41589-019-0337-z

Asymmetric cell division, which generates daughter cells with distinct characteristics, is a mechanism for creating complex systems through cellular differentiation. Two studies in this issue develop synthetic platforms that program spatial localization of genetic material or signaling molecules to enable asymmetric cell division in Escherichia coli.