Interrogating Interactions and Modifications of Histones in Live Cells

Abstract

In this issue of Cell Chemical Biology, new methods are reported to interrogate histone interactions and modifications. Kleiner et al. (2018) develop a chemical proteomics platform for profiling of direct, context-dependent histone-protein interactions in living cells, and Delachat et al. (2018) engineer fluorescent sensors for coexisting histone modifications in live stem cells.

Cereblon versus VHL: Hijacking E3 ligases against each other using PROTACs

“… 11 , 12 , 13 , 14 Furthermore, PROTAC’s selectivity can be greater than the binding selectivity of the ligands alone, allowing to discriminate between highly similar proteins or isoforms in ways that are not possible with occupancy-based inhibitors. 8 , 11 , 12 , 15 , 16 , 17 Within the past four years, potent and selective PROTACs have been designed to hijack either the von Hippel-Lindau (VHL) or cereblon (CRBN) E3 ligase against a target protein of interest. 18 , 19 Targets that have been shown to be degraded by PROTACs include members of bromodomain-containing proteins such as the BET proteins (Brd2, Brd3 and Brd4), 7 , 8 , 9 , 14 , 15 , 17 , 20 , 21 amongst other epigenetic protein classes; 22 , 23 , 24 , 25 , 26 protein kinases; 10 , 12 , 27 , 28 , 29 , 30 , 31 as well as non-bromodomain and non-kinase target proteins.…”

“…Because their mode of action differs from that of conventional inhibitors, the concentrations at which PROTACs exert degradation activity are often much lower than expected based on their dissociation constants with the target protein 11, 12, 13, 14. Furthermore, PROTAC’s selectivity can be greater than the binding selectivity of the ligands alone, allowing to discriminate between highly similar proteins or isoforms in ways that are not possible with occupancy-based inhibitors 8, 11, 12, 15, 16, 17. Within the past four years, potent and selective PROTACs have been designed to hijack either the von Hippel-Lindau (VHL) or cereblon (CRBN) E3 ligase against a target protein of interest 18, 19.…”

H2S and reactive sulfur signaling at the host-bacterial pathogen interface

“…Their Janus character, enhanced nucleophilicity, and superior reducing capabilities make RSSH, along with organic polysulfides and their inorganic counterparts, potent antioxidants (Fig. 1B, bottom) (43,51,52). These properties may well be responsible for many of the beneficial traits attributed to H 2 S, including protection against oxidative stress and antibiotics in the infected host (21,26,47).…”

Comparative Study of Protective Action of Exogenous 2-Cys Peroxiredoxins (Prx1 and Prx2) Under Renal Ischemia-Reperfusion Injury

“…Previously, it has been shown that Prx1, Prx2, Prx5 and Prx6 are potent DAMPs in ischemic stroke, with TLR4 being their main recognition receptor. Through interaction with the TLR4 receptor, peroxiredoxins (Prx1, Prx2, Prx5 and Prx6) express pro-inflammatory/regenerative factors via the TLR4/MyD88/NF-kB signaling pathway [ 14 , 73 , 74 , 75 , 76 , 77 , 78 , 79 ]. Moreover, we suggest that intravenous injection of recombinant Prx1 or Prx2 in animals before renal I/R injury can provide a preconditioning effect, through stimulation of the TLR4/NF-kB signaling pathway.…”