DNAJA3, a Co-chaperone in Development and Tumorigenesis
Introduction: DNAJA3, also known as Tid1 (Tumorous imaginal disc 1), is a mammalian mitochondrial DNAJ/HSP40 co-chaperone protein. DNAJA3 is predominantly localized in mitochondrial matrix which enables them to interact with mitochondrial HSP70 or other c
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Abstract Introduction: DNAJA3, also known as Tid1 (Tumorous imaginal disc 1), is a mammalian mitochondrial DNAJ/HSP40 co-chaperone protein. DNAJA3 is predominantly localized in mitochondrial matrix which enables them to interact with mitochondrial HSP70 or other client proteins. This chapter summarizes the physiological and biochemical functions of DNAJA3 in tumorigenesis, development and mitochondrial homeostasis, and its underlying molecular mechanisms. Methods: All literatures were systematically searched through EndNote and web search engines. The reported discoveries and our findings were specifically categorized into multiple roles of DNAJA3. Results: DNAJA3 has been identified as tumor suppressor. Overexpression of DNAJA3 not only inhibits cancer cells proliferation but also induces cells death. In opposite, downregulation of DNAJA3 enhances malignant properties such as cell migration and invasion in vitro, and tumor growth in vivo. Acting as a tumor suppressor, DNAJA3 can interfere with the matrix metalloproteinase to repress the cancer metastasis. Additionally, DNAJA3 is involved in early embryogenesis, thymocyte development, muscular development and mitochondrial biogenesis in normal physiological condition. Mechanistically, DNAJA3 interacts with DNAK/
W.-H. Teo Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan Y.-N. Fann Department & Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan J.-F. Lo (*) Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan Department & Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan Cancer Progression Research Center, National Yang-Ming University, Taipei, Taiwan e-mail: jfl[email protected] © Springer Nature Switzerland AG 2020 A. A. A. Asea, P. Kaur (eds.), Heat Shock Proteins, https://doi.org/10.1007/7515_2020_33
W.-H. Teo et al.
HSP70 to prevent aggregation of mitochondrial complex I and to contribute mtDNA maintenance. Conclusions: Most of DNAJA3 client proteins are related to cancer. Therefore, it is of the importance of DNAJA3 to orchestrate its function in tumorigenesis. DNAJA3 also important in development and mitochondrial homeostasis. Keywords DNAJA3 · HSP40 · HSP70 · Mitochondrial homeostasis · T cells development · Tid1 · Tumor suppressor
Abbreviations APC CRC Cyt DCM EBV EGFR EOPD ER HBV HCC hERG HGF HNSCC HSP HSV HTLV-1 MEF Mem MetR Mito NSCLC Opa1 RCC-CICs Tid1 TNFα VHL YY1
Adenomatous polyposis coli Colorectal cancer Cytoplasmic Dilated cardiomyopathy Epstein-Barr virus Epidermal growth factor receptor Early onset Parkinson’s Endoplasmic reticulum Hepatitis B virus Hepatocellular carcinoma Human ether-a-go-go-related gene Hepatocyte growth factor Head and neck squamous cell carcinoma Heat shock protein Herpes simplex virus type 1 Human T cell leukemia virus type 1 Mouse embryonic fibroblast Membrane c-Met receptor tyrosine kinase Mitochondria Non-small cell lung carcinoma Optic atrophy 1 Renal cell carcinoma cancer- initiating cells Tumorous imaginal disc 1 Tumor necrosis factor
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