Hsp70-Hsp90 organising protein (HOP/STIP1) is required for KSHV lytic replication.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a DNA virus that causes Kaposi's sarcoma, a cancer of endothelial origin. KSHV uses the activity of host molecular chaperones like Hsp70 and Hsp90 for the folding of host and viral proteins required for productive infection. Hsp70 and Hsp90 chaperones form proteostasis networks with several regulatory proteins known as co-chaperones.

Mutations F352A and Y528A in human HSP90α reduce fibronectin association and fibrillogenesis in cell-derived matrices.

HSP90 is a ubiquitously expressed chaperone protein that regulates the maturation of numerous substrate proteins called 'clients'. The glycoprotein fibronectin (FN) is an important protein of the extracellular matrix (ECM) and a client protein of HSP90. FN and HSP90 interact directly, and the FN ECM is regulated by exogenous HSP90 or HSP90 inhibitors.

Comparative Analyses of Fucoidans from South African Brown Seaweeds That Inhibit Adhesion, Migration, and Long-Term Survival of Colorectal Cancer Cells.

Human colorectal cancer (CRC) is a recurrent, deadly malignant tumour with a high incidence. The incidence of CRC is of increasing alarm in highly developed countries, as well as in middle to low-income countries, posing a significant global health challenge. Therefore, novel management and prevention strategies are vital in reducing the morbidity and mortality of CRC.

Hsp70/Hsp90 Organising Protein (Hop): Coordinating Much More than Chaperones.

The Hsp70/Hsp90 organising protein (Hop, also known as stress-inducible protein 1/STI1/STIP1) has received considerable attention for diverse cellular functions in both healthy and diseased states. There is extensive evidence that intracellular Hop is a co-chaperone of the major chaperones Hsp70 and Hsp90, playing an important role in the productive folding of Hsp90 client proteins, although recent evidence suggests that eukaryotic Hop is regulatory within chaperone complexes rather than essential. Consequently, Hop is implicated in many key signalling pathways, including aberrant pathways leading to cancer.

analysis of the HSP90 chaperone system from the African trypanosome, .

African trypanosomiasis is a neglected tropical disease caused by () and spread by the tsetse fly in sub-Saharan Africa. The trypanosome relies on heat shock proteins for survival in the insect vector and mammalian host. Heat shock protein 90 (HSP90) plays a crucial role in the stress response at the cellular level.

HSP90 as a regulator of extracellular matrix dynamics.

The extracellular matrix (ECM) is a dynamic and organised extracellular network assembled from proteins and carbohydrates exported from the cell. The ECM is critical for multicellular life, providing spatial and temporal cellular cues to maintain tissue homeostasis. Consequently, ECM production must be carefully balanced with turnover to ensure homeostasis; ECM dysfunction culminates in disease.

A Combination Approach in Inhibiting Type 2 Diabetes-Related Enzymes Using Fucoidan and Acarbose.

Although there are chemotherapeutic efforts in place for Type 2 diabetes mellitus (T2DM), there is a need for novel strategies (including natural products) to manage T2DM. Fucoidan, a sulphated polysaccharide was extracted from . The integrity of the fucoidan was confirmed by structural analysis techniques such as FT-IR, NMR and TGA.

General Structural and Functional Features of Molecular Chaperones.

Molecular chaperones are a group of structurally diverse and highly conserved ubiquitous proteins. They play crucial roles in facilitating the correct folding of proteins in vivo by preventing protein aggregation or facilitating the appropriate folding and assembly of proteins. Heat shock proteins form the major class of molecular chaperones that are responsible for protein folding events in the cell.

Nonspecific nuclear uptake of anti-MUC1 aptamers by dead cells: the role of cell viability monitoring in aptamer targeting of membrane-bound protein cancer biomarkers.

Most aptamers targeting cell-expressed antigens are intended for in vivo application, however, these sequences are commonly generated in vitro against synthetic oligopeptide epitopes or recombinant proteins. As these in vitro analogues frequently do not mimic the in vivo target within an endogenous environment, the evolved aptamers are often prone to nonspecific binding. The presence of dead cells and cellular debris further complicate aptamer targeting, due to their high nonspecific affinities to single-stranded DNA.

Fucoidan Structure and Its Impact on Glucose Metabolism: Implications for Diabetes and Cancer Therapy.

Fucoidans are complex polysaccharides derived from brown seaweeds which consist of considerable proportions of L-fucose and other monosaccharides, and sulphated ester residues. The search for novel and natural bioproduct drugs (due to toxicity issues associated with chemotherapeutics) has led to the extensive study of fucoidan due to reports of it having several bioactive characteristics. Among other fucoidan bioactivities, antidiabetic and anticancer properties have received the most research attention in the past decade.

Ruthenium complexes with or -heterocyclic chelates: DNA/BSA binding, antioxidant and anticancer studies.

Deoxyribonucleic acid (DNA) and bovine serum albumin (BSA) binding interactions for a series of ruthenium heterocyclic complexes were monitored using ultraviolet-visible (UV-Vis) spectrophotometry, fluorescence emission spectroscopy and agarose gel electrophoresis. Investigations of the DNA interactions for the metal complexes revealed that they are groove-binders with intrinsic binding constants in the order of 10 - 10 . Electronic spectrophotometric DNA titrations of the -heterocyclic metal complexes illustrated hypochromism of their intraligand electronic transitions and the presence of diffuse isosbestic points which are synonymous with homogeneous binding modes.

Author Correction: LRP1 is required for novobiocin-mediated fibronectin turnover.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

STIP1/HOP Regulates the Actin Cytoskeleton through Interactions with Actin and Changes in Actin-Binding Proteins Cofilin and Profilin.

Cell migration plays a vital role in both health and disease. It is driven by reorganization of the actin cytoskeleton, which is regulated by actin-binding proteins cofilin and profilin. Stress-inducible phosphoprotein 1 (STIP1) is a well-described co-chaperone of the Hsp90 chaperone system, and our findings identify a potential regulatory role of STIP1 in actin dynamics.

Hop depletion reduces HSF1 levels and activity and coincides with reduced stress resilience.

Heat-shock factor 1 (HSF1) regulates the transcriptional response to stress and controls expression of molecular chaperones required for cell survival. Here we report that HSF1 is regulated by the abundance of the Hsp70-Hsp90 organizing protein (Hop/STIP1). HSF1 levels were significantly reduced in Hop-depleted HEK293T cells.

HSP90 Interacts with the Fibronectin N-terminal Domains and Increases Matrix Formation.

Heat shock protein 90 (HSP90) is an evolutionarily conserved chaperone protein that controls the function and stability of a wide range of cellular client proteins. Fibronectin (FN) is an extracellular client protein of HSP90, and exogenous HSP90 or inhibitors of HSP90 alter the morphology of the extracellular matrix. Here, we further characterized the HSP90 and FN interaction.

Hop/STIP1 depletion alters nuclear structure via depletion of nuclear structural protein emerin.

Hop/STIP1 is a co-chaperone of Hsp70 and Hsp90 that regulates a number of cell biology processes via interactions with cellular proteins. Here we report a new relationship between Hop and the nuclear structural protein emerin in maintenance of nuclear morphology. Depletion or overexpression of Hop resulted in the reduction of emerin protein levels via proteasomal and lysosomal pathways.

LRP1 is required for novobiocin-mediated fibronectin turnover.

Fibronectin (FN) plays a major role in the stability and organization of the extracellular matrix (ECM). We have previously demonstrated that FN interacts directly with Hsp90, as well as showing that the Hsp90 inhibitor novobiocin results in FN turnover via a receptor mediated process. However, the receptor involved has not been previously identified.

analysis of putative cancer stem cell populations and chemosensitivity in the SW480 and SW620 colon cancer metastasis model.

The cancer stem cell (CSC) theory implicates a small subpopulation of cells with stem-like properties, which is responsible for tumour initiation, development and metastasis. The unique biological and functional characteristics of CSCs, widely associated with treatment resistance, indicate an association between metastasis and stemness. It was hypothesised that metastatic cell lines may be enriched in CSCs and that this would correlate with a more resistant tumour.

Heterodimer formation by Oct4 and Smad3 differentially regulates epithelial-to-mesenchymal transition-associated factors in breast cancer progression.

The multifunctional cytokine TGF-β crucially participates in breast cancer (BCa) metastasis and works differently in the disease stages, thus contributing in BCa progression. We address connections between TGF-β and the stem cell-related transcription factor (TF) Oct4 in BCa. In 147 BCa patients with infiltrating duct carcinoma, we identified a significantly higher number of cases with both moderate/high Oct4 expression and high TGF-β in late stages compared to early stages of the disease.

Fibronectin is a stress responsive gene regulated by HSF1 in response to geldanamycin.

Fibronectin is an extracellular matrix glycoprotein with key roles in cell adhesion and migration. Hsp90 binds directly to fibronectin and Hsp90 depletion regulates fibronectin matrix stability. Where inhibition of Hsp90 with a C-terminal inhibitor, novobiocin, reduced the fibronectin matrix, treatment with an N-terminal inhibitor, geldanamycin, increased fibronectin levels.

Sequence and domain conservation of the coelacanth Hsp40 and Hsp90 chaperones suggests conservation of function.

Molecular chaperones and their associated co-chaperones play an important role in preserving and regulating the active conformational state of cellular proteins. The chaperone complement of the Indonesian Coelacanth, Latimeria menadoensis, was elucidated using transcriptomic sequences. Heat shock protein 90 (Hsp90) and heat shock protein 40 (Hsp40) chaperones, and associated co-chaperones were focused on, and homologous human sequences were used to search the sequence databases.