Biology subjects

Bury, K.

Publications and source records attributed to Bury, K..

3 recordsLinked to original sources

bioRxiv2026

β4-integrins safeguard nuclear mechanics to suppress prostate cancer progression

Prostate cancer (PCa) progression is accompanied by profound alterations in cell-extracellular matrix (ECM) adhesion, nuclear architecture and mechanical adaptability, yet the molecular mechanisms linking these processes remain poorly understood. Hemidesmosomes (HDs), formed by 6{beta}4-integrins, anchor epithelial cells to the basement membrane and couple extracellular forces to the intermediate filament (IF) cytoskeleton. Here, we identify a previously unrecognized tumor-suppressive function of {beta}4-integrins in preserving nuclear integrity in prostate epithelial cells. Loss of {beta}4-integrins disrupted the cytokeratin-5 network and its coupling to the nucleus, leading to nuclear softening, lamin remodeling, reduced heterochromatin content and enhanced confined migration. Unexpectedly, proximity-labeling proteomics revealed that {beta}4-integrins engage nuclear pore complex (NPC) components in an 6-independent manner, particularly upon HD disassembly. Selected interactions were validated using proximity ligation and co-immunoprecipitation assays. {beta}4-integrin loss was associated with enlarged nuclear pores and aberrant nucleocytoplasmic transport, including nuclear accumulation of YAP1. Consistent with these findings, reduced {beta}4-integrin expression in a large PCa tissue cohort correlated with altered nuclear morphology, adverse clinicopathological features, metastatic progression, and poor patient survival. Collectively, our study establishes {beta}4-integrins as a critical molecular link between cell-ECM adhesion, nuclear mechanics and genome integrity.

cancer biology↗

bioRxiv2025

Origin of Class B J-domain proteins involved in amyloid transactions

J-domain protein (JDP) chaperones function widely in proteostasis. Notably, eukaryotic class B JDPs of the cytosol/nucleus prevent assembly or drive disassembly of amyloid aggregates known to cause neurodegenerative diseases, yet their evolutionary origin is not known. Members of the most ubiquitous class B subgroup, canonical B (BC) JDPs, lack the signature zinc finger region (ZnF) of the more prevalent class A JDPs, while having other key features in common. Our phylogenetic analysis revealed that BC JDPs evolved more than once from class A duplicates, losing their ZnF. The cytonuclear BCs emerged at the base of eukaryotes. Cytonuclear class B (i.e. B(ST)) JDPs that have a substrate binding domain of unknown origin, distinct from that of As and BCs, emerged from a BC duplication at the base of metazoans and subsequently multiplied by duplications. Origin of B(ST)s, which are capable of suppressing formation of amyloid aggregates, predated the emergence of disease-causing amyloidogenic proteins. Using ancestral sequence resurrection, we tested when cytonuclear Bs evolved their amyloid related functions. We found that their common ancestor with As, AncAB that has a ZnF does not facilitate disassembly of amyloid fibrils, while AncB, which lacks a ZnF, is active. Overall, our findings are consistent with the idea that, though the ZnF of class A JDPs is important for some roles, its loss allowed evolution of novel functions, as illustrated by the ability of BC and B(ST) JDPs to control amyloid aggregate levels. Significance statementAcross procaryotes and eukaryotes J-domain proteins (JDPs) are key players in Hsp70 chaperone systems that maintain cellular protein homeostasis. The abundant class A and B JDPs have structural similarities, yet their origin has remained unresolved. Here we show that B JDPs independently evolved from As more than once. In each case A lost its zinc finger (ZnF) domain, suggesting that such loss has allowed evolution of new functions. Supporting this idea, biochemical resurrection of an ancestral eukaryotic B revealed that its ability to disassemble amyloid aggregates, differentiating it from As, evolved after ZnF loss. Later, the subset of Bs implicated in suppression of disease-causing amyloid aggregate formation originated from a duplicate of this B in the common ancestor of animals.

evolutionary biology↗

bioRxiv2020

Lsr2 is a nucleoid-associated protein that exerts pleiotropic effects on mycobacterial cellular processes

Lsr2 is involved in maintaining chromosome structure in asymmetrically dividing mycobacteria and is essential in the tubercle bacillus (M. tuberculosis) during infection. Here, we report that a lack of Lsr2 profoundly impacts the mycobacterial cell morphology and the properties of the cell envelope resulting in the formation of smooth, short and antibiotics sensitive cells. Lsr2 forms large and dynamic nucleoprotein complexes in vivo and deletion of lsr2 gene exerts a profound effect on the replication time and replisome dynamics. We suggest that the Lsr2 nucleoprotein complexes may contribute to maintaining the proper organization of the newly synthesized DNA. Moreover, we demonstrate that the N-terminal oligomerization domain of Lsr2 is indispensable for the formation of nucleoprotein complexes in vivo. Collectively, our results indicate that Lsr2 exerts a pleiotropic effect on cellular processes and appears to be an attractive target for the development of a novel antitubercular drugs.

microbiology↗