DOI: 10.1101/506881Dec 27, 2018Paper

HSF2 protects against proteotoxicity by maintaining cell-cell adhesion

BioRxiv : the Preprint Server for Biology
Jenny JoutsenL Sistonen


Cellular ability to maintain proper protein homeostasis (proteostasis) is essential for survival upon protein-damaging conditions. Heat shock transcription factor 2 (HSF2) is one of the human HSFs activated in response to proteotoxic stress. HSF2 is dispensable for cell survival during acute heat stress, but its amount and DNA-binding activity increase under prolonged proteotoxic stress conditions, such as proteasome inhibition. Nevertheless, the specific role(s) of HSF2 and the global HSF2-dependent gene expression profile during sustained stress have remained elusive. We found that HSF2 is required for cell survival during prolonged proteotoxicity, as shown by treating wild-type and HSF2-deficient human osteosarcoma U2OS cells with the proteasome inhibitor Bortezomib. Strikingly, our RNA-seq analyses revealed that HSF2 disruption leads to marked downregulation of cadherin superfamily genes and subsequent functional impairment of cadherin-mediated cell-cell adhesion. We propose HSF2 as a key regulator of genes belonging to the cadherin superfamily. We also demonstrate that HSF2-dependent downregulation of cadherin-mediated cell-cell adhesion predisposes U2OS cells to Bortezomib-induced proteotoxic stress. In conclusion, we sho...Continue Reading

Related Concepts

Tissue Adhesions
Cell Survival
Gene Expression
Heat shock transcription factor
HSF2 protein, human
Sequence Analysis, RNA

Related Feeds

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.

Cadherins and Catenins

Cadherins (named for "calcium-dependent adhesion") are a type of cell adhesion molecule (CAM) that is important in the formation of adherens junctions to bind cells with each other. Catenins are a family of proteins found in complexes with cadherin cell adhesion molecules of animal cells: alpha-catenin can bind to β-catenin and can also bind actin. β-catenin binds the cytoplasmic domain of some cadherins. Discover the latest research on cadherins and catenins here.

Adherens Junctions

An adherens junction is defined as a cell junction whose cytoplasmic face is linked to the actin cytoskeleton. They can appear as bands encircling the cell (zonula adherens) or as spots of attachment to the extracellular matrix (adhesion plaques). Adherens junctions uniquely disassemble in uterine epithelial cells to allow the blastocyst to penetrate between epithelial cells. Discover the latest research on adherens junctions here.

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.