Müller, C. S. | bioRxiv Science

bioRxiv2024

Structural basis of dual BACH1 regulation by SCFFBXO22 and SCFFBXL17

BTB and CNC homolog 1 (BACH1) is a master transcriptional regulator of the cellular oxidative stress response and pro-metastatic oncogene. Post-translational stability of BACH1 is tightly regulated by distinct F-box ubiquitin ligases, including SCFFBXO22 and SCFFBXL17. However, the molecular details have been elusive. Here, we reveal a structural switch in FBXO22 that controls the recognition of a three-dimensional degron in the BACH1 BTB domain, thus explaining its specificity for dimeric BACH1. We describe how cancer-associated mutations in FBXO22 modulate binding and ubiquitylation of BACH1. Further, we reveal that cancer-related mutations or cysteine-modifications destabilize the BTB domain and redirect BACH1 to FBXL17, where it is recognized as a monomer. This explains how complementary ligases post-translationally regulate BACH1 depending on the state of its BTB domain. Our findings provide mechanistic insights into the regulation of the oxidative stress response and may spur therapeutic strategies to targeting oxidative stress-related disorders and metastatic cancers.

biophysics↗

bioRxiv2018

Environment-driven genomic and trait divergence in a neotropical mangrove highlight differential sensitivities to climate change

Local adaptation is often a product of environmental variations in the geographical space and has implications for biodiversity conservation. We investigated the role of latitudinal heterogeneity in climate on the organization of genetic and phenotypic variation in the dominant coastal tree, Avicennia schaueriana. In a common garden experiment, samples from an equatorial region, marked by rainy/dry seasons, accumulated less biomass, showed lower stomatal conductance and transpiration, narrower xylem vessels, smaller leaves and higher reflectance of long wavelengths (red light) on the stem epidermis, than samples from a subtropical region, marked by warm/cold seasons. Transcriptome differences identified between trees sampled under field conditions at equatorial and subtropical sites, were enriched in functional categories as responses to temperature, solar radiation, water deficit, photosynthesis and cell wall biosynthesis. The diversity based on thousands of SNP loci revealed a north-south genetic structure. Remarkably, signatures of selection were identified in loci associated with photosynthesis, anthocyanin accumulation and the responses to osmotic and hypoxia stresses. Our results suggest the existence of divergence in key resource-use characteristics, likely driven by climate seasonality, based on water-deficit and solar radiation. These findings provide a basis for conservation plans and for predictions for coastal plant responses to climate change.

plant biology↗