Biology subjects

Darling, S.

Publications and source records attributed to Darling, S..

2 recordsLinked to original sources

bioRxiv2021

S18-phosphorylation of USP7 regulates interaction with TCEAL4 that defines specific complexes and potentially distinct functions.

USP7 is a nuclear deubiquitylase (DUB) with multiple cancer-associated substrates for which selective inhibitors are available, yet it remains unclear how the pleiotropic effects of USP7 are regulated. We report that S18-phosphorylation does not influence USP7 catalytic activity but instead confers selectivity for protein interactions. In particular, non-S18-phosphorylatable USP7 preferentially interacts with USP11 and TRIM27, together with TCEAL1 and TCEAL4 whose functions are unknown. Intriguingly, USP7 can interact with two cellular forms of TCEAL4, but USP11 only interacts with a lower abundance K142 mono-ubiquitylated form (TCEAL4-Ub), which can scaffold a complex containing both DUBs. Whilst USP11 and TCEAL4 are both USP7 substrates, TCEAL4-Ub levels are specifically maintained by USP11 with their levels positively correlated in cancer cell lines. Together these data illustrate how USP7 phosphorylation and TCEAL4 ubiquitylation combine to define distinct USP7 complexes. As TCEAL4 itself interacts with proteins involved in ubiquitylation and various forms of DNA regulation, these complexes may direct cellular activity of USP7.

cell biology↗

bioRxiv2021

Environmental transmission of Pseudogymnoascus destructans to hibernating little brown bats

Pathogens with persistent environmental stages can have devastating effects on wildlife communities. White-nose syndrome (WNS), caused by the fungus Pseudogymnoascus destructans, has caused widespread declines in bat populations of North America. In 2009, during the early stages of the WNS investigation and before molecular techniques had been developed to readily detect P. destructans in environmental samples, we initiated this study to assess whether P. destructans can persist in the hibernaculum environment in the absence of its conclusive bat host and cause infections in naive bats. We transferred little brown bats (Myotis lucifugus) from an unaffected winter colony in northwest Wisconsin to two P. destructans contaminated hibernacula in Vermont where native bats had been excluded. Infection with P. destructans was apparent on some bats within 8 weeks following the introduction of unexposed bats to these environments, and mortality from WNS was confirmed by histopathology at both sites 14 weeks following introduction. These results indicate that environmental exposure to P. destructans is sufficient to cause the infection and mortality associated with WNS in naive bats, which increases the probability of winter colony extirpation and complicates conservation efforts.

ecology↗