Heat shock proteins (HSPs) are highly conserved molecular chaperones with diverse cellular activities, including protein folding, assembly or disassembly of protein complexes, and maturation process under diverse stress conditions. HSPs also play essential roles in tumorigenesis, metastasis, and therapeutic resistance across cancers. Among them, HSP40s are widely accepted as regulators of HSP70/HSP90 chaperones and an accumulating number of biological functions as molecular chaperones dependent or independent of either of these chaperones. Despite large numbers of HSP40s, little is known about their physiologic roles, specifically in cancer progression. This article summarizes the multi-faceted role of DNAJB proteins as one subclass of the HSP40 family in cancer development and metastasis. Regulation and deregulation of DNAJB proteins at transcriptional, post-transcriptional, and post-translational levels contribute to tumor progression, particularly cancer metastasis. Furthermore, understanding differences in function and regulating mechanism between DNAJB proteins offers a new perspective on tumorigenesis and metastasis to improve therapeutic opportunities for malignant diseases.
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http://dx.doi.org/10.3390/ijms232314970 | DOI Listing |
Cell Stress Chaperones
April 2024
Institute of Physics, School of Basic Sciences, École Polytechnique Fédérale de Lausanne - EPFL, 1015 Lausanne, Vaud, Switzerland; Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne - EPFL, 1015 Lausanne, Vaud, Switzerland. Electronic address:
The 70 kDa heat shock protein (Hsp70) chaperones control protein homeostasis in all ATP-containing cellular compartments. J-domain proteins (JDPs) coevolved with Hsp70s to trigger ATP hydrolysis and catalytically upload various substrate polypeptides in need to be structurally modified by the chaperone. Here, we measured the protein disaggregation and refolding activities of the main yeast cytosolic Hsp70, Ssa1, in the presence of its most abundant JDPs, Sis1 and Ydj1, and two swap mutants, in which the J-domains have been interchanged.
View Article and Find Full Text PDFCureus
January 2023
Surgery and Anatomy, Hospital das Clinicas - Faculdade de Medicina de Ribeirão Preto, Ribeirão Preto, BRA.
Hyperammonemic encephalopathy is a potentially fatal condition associated with fibrolamellar hepatocellular carcinoma. The mechanism involved in hyperammonemia in patients with fibrolamellar carcinoma was unclear until a possible physiopathological pathway was recently proposed. An ornithine transcarboxylase dysfunction was suggested as a result of increased ornithine decarboxylase activity induced by c-Myc overexpression.
View Article and Find Full Text PDFBr J Cancer
March 2023
Department of Pathology, Sapporo Medical University, School of Medicine, South-1, West-17, Chuo-ku, Sapporo, Hokkaido, 060-8556, Japan.
Background: As therapy for solid tumours, various tumour antigens have been selected as targets, but CAR-T cells targeting these antigens have shown limited efficacy, in contrast to the effectiveness of CAR-T cells targeting haematological malignancies. In a previous report, we identified a cancer-testis antigen, DNAJB8. DNAJB8 plays a major role in tumorigenicity in cancer stem-like cells/cancer-initiating cells (CSCs/CICs).
View Article and Find Full Text PDFInt J Mol Sci
November 2022
Laboratory of Cancer Cell Biology, Department of Biochemistry, Gachon University School of Medicine, 155 Gaetbel-ro Yeonsu-gu, Incheon 21999, Republic of Korea.
Heat shock proteins (HSPs) are highly conserved molecular chaperones with diverse cellular activities, including protein folding, assembly or disassembly of protein complexes, and maturation process under diverse stress conditions. HSPs also play essential roles in tumorigenesis, metastasis, and therapeutic resistance across cancers. Among them, HSP40s are widely accepted as regulators of HSP70/HSP90 chaperones and an accumulating number of biological functions as molecular chaperones dependent or independent of either of these chaperones.
View Article and Find Full Text PDFActa Neuropathol
January 2023
John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
DNAJ/HSP40 co-chaperones are integral to the chaperone network, bind client proteins and recruit them to HSP70 for folding. We performed exome sequencing on patients with a presumed hereditary muscle disease and no genetic diagnosis. This identified four individuals from three unrelated families carrying an unreported homozygous stop gain (c.
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