CCAR2/DBC1 and Hsp60 Positively Regulate Expression of Survivin in Neuroblastoma Cells

Kim, Wootae; Ryu, Jaewook; Kim, Ja-Eun

doi:10.3390/ijms20010131

Cited by 34 publications

(26 citation statements)

References 61 publications

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“…Nevertheless, the molecular stabilization effect of survivin through the formation of cytosolic HSP60-survivin complex in HCC cells is the same as what has occurred in breast cancer cells [12]. No matter where the HSP60-survivin interaction occurs, cytosol or mitochondria, the amounts of these two molecules are positively correlated [9,12,29,34]. Decreased expression of HSP60 leads to a decrease of survivin levels that eventually causes cell death [9,12].…”

Section: Hsp60-survivin Interactionmentioning

confidence: 88%

“…Additionally, CCAR2 binds to survivin in the absence of mitochondrial stress, and CCAR2-HSP60 complexes increase upon mitochondria stress. In this view, CCAR2 sequesters survivin and brings it to HSP60 in mitochondria, allowing HSP60 to stabilize survivin [29,54].…”

Section: Interaction Between Hsp60 and Survivin In Mitochondriamentioning

confidence: 99%

“…The study by Kim et al has demonstrated the formation of CCAR2-HSP60-survivin complex, while no detailed experiments were performed to explore the fates of the complex upon death stimuli. [29] A review by Kelly et al suggested chaperone binding to survivin could form a stabilized complex. [58] Therefore, it remains possible that the heterocomplex could stabilize both proteins, whereas upon death stimuli, other factors might join in to destabilize them, leading to survivin degradation via ubiquitination.…”

Section: Interaction Between Hsp60 and Survivin In Cytosolmentioning

confidence: 99%

“…As such, many similar biofunctions exist between HSP60 and survivin. In addition, a positive correlation has been demonstrated between their expression levels [12,29]. Nevertheless, our knowledge regarding the function of HSP60-survivin complex and the molecular events involved in tumor cells during apoptosis remains limited.…”

Section: Introductionmentioning

confidence: 99%

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Functional Compartmentalization of HSP60-Survivin Interaction between Mitochondria and Cytosol in Cancer Cells

Huang

Yeh

2019

Cells

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Heat shock protein 60 (HSP60) and survivin reside in both the cytosolic and mitochondrial compartments under physiological conditions. They can form HSP60-survivin complexes through protein-protein interactions. Their expression levels in cancer tissues are positively correlated and higher expression of either protein is associated with poor clinical prognosis. The subcellular location of HSP60-survivin complex in either the cytosol or mitochondria is cell type-dependent, while the biological significance of HSP60-survivin interaction remains elusive. Current knowledge indicates that the function of HSP60 partly rests on where HSP60-survivin interaction takes place. HSP60 has a pro-survival function when binding to survivin in the mitochondria through interacting with other factors such as CCAR2 and p53. In response to cell death signals, mitochondrial survivin functions through preventing procaspase activation. Degradation of cytosolic survivin leads to the loss of mitochondrial membrane potential and aberrant mitosis processes. On the other hand, HSP60 release from mitochondria to cytosol upon death stimuli might exert a pro-death function, either through stabilizing Bax, enhancing procaspase-3 activation, or increasing protein ubiquitination. Combining the knowledge of mitochondrial HSP60-survivin complex function, cytosolic survivin degradation effect, and pro-death function upon mitochondria release of HSP60, a hypothetical scenario for HSP60-survivin shuttling upon death stimuli is proposed.

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Section: Hsp60-survivin Interactionmentioning

confidence: 88%

Section: Interaction Between Hsp60 and Survivin In Mitochondriamentioning

confidence: 99%

Section: Interaction Between Hsp60 and Survivin In Cytosolmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Functional Compartmentalization of HSP60-Survivin Interaction between Mitochondria and Cytosol in Cancer Cells

Huang

Yeh

2019

Cells

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“…In turn, p53 n further upregulates Bax and induces the pro-apoptotic brain-expressed X-linked (Bex) genes [ 75 , 77 ]. Moreover, downregulation of mitochondrial Hsp60 allows for the upregulation of cytosolic p53 (p53 c ), which in turn downregulates the pro-survival protein Survivin [ 78 ].…”

Section: Curcumin As An Anticancer Agent In Nbmentioning

confidence: 99%

Curcumin’s Beneficial Effects on Neuroblastoma: Mechanisms, Challenges, and Potential Solutions

et al. 2020

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Curcumin, a natural polyphenolic compound derived from the South Asian turmeric plant (Curcuma longa), has well-characterized antioxidant, anti-inflammatory, anti-protein-aggregate, and anticancer properties. Neuroblastoma (NB) is a cancer of the nervous system that arises primarily in pediatric patients. In order to reduce the multiple disadvantages and side effects of conventional oncologic modalities and to potentially overcome cancer drug resistance, natural substances such as curcumin are examined as complementary and supportive therapies against NB. In NB cell lines, curcumin by itself promotes apoptosis and cell cycle arrest through the suppression of serine–threonine kinase Akt and nuclear factor kappa of activated B-cells (NF-κB) signaling, induction of mitochondrial dysfunction, and upregulation of p53 and caspase signaling. While curcumin demonstrates anti-NB efficacy in vitro, cross-validation between NB cell types is currently lacking for many of its specific mechanistic activities. Furthermore, curcumin’s low bioavailability by oral administration, poor absorption, and relative insolubility in water pose challenges to its clinical introduction. Numerous curcumin formulations, including nanoparticles, nanocarriers, and microemulsions, have been developed, with these having some success in the treatment of NB. In the future, standardization and further basic and preclinical trials will be required to ensure the safety of curcumin formulations. While the administration of curcumin is clinically safe even at high doses, clinical trials are necessary to substantiate the practical efficacy of curcumin in the prevention and treatment of NB.

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Molecular mechanisms in chaperonopathies: clues to understanding the histopathological abnormalities and developing novel therapies

Macario

2019

The Journal of Pathology

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Molecular chaperones, many of which are heat shock proteins (Hsps), are components of the chaperoning system and when defective can cause disease, the chaperonopathies. Chaperone-gene variants cause genetic chaperonopathies, whereas in the acquired chaperonopathies the genes are normal, but their protein products are not, due to aberrant post-transcriptional mechanisms, e.g. post-translational modifications (PTMs). Since the chaperoning system is widespread in the body, chaperonopathies affect various tissues and organs, making these diseases of interest to a wide range of medical specialties. Genetic chaperonopathies are uncommon but the acquired ones are frequent, encompassing various types of cancer, and inflammatory and autoimmune disorders. The clinical picture of chaperonopathies is known. Much less is known on the impact that pathogenic mutations and PTMs have on the properties and functions of chaperone molecules. Elucidation of these molecular alterations is necessary for understanding the mechanisms underpinning the tissue and organ abnormalities occurring in patients. To illustrate this issue, we discuss structural-functional alterations caused by mutation in the chaperones CCT5 and HSPA9, and PTM effects on Hsp60. The data provide insights into what may happen when CCT5 and HSPA9 malfunction in patients, e.g. accumulation of cytotoxic protein aggregates with tissue destruction; or for Hsp60 with aberrant PTM, degradation and/or secretion of the chaperonin with mitochondrial damage. These and other possibilities are now open for investigation.The canonical functions of chaperones pertain to the maintenance of protein homeostasis, in essence protein-quality control; for example: assisting in the correct folding of nascent polypeptides, ushering polypeptides to their place of residence including through membranes, helping partially denatured

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CCAR2/DBC1 and Hsp60 Positively Regulate Expression of Survivin in Neuroblastoma Cells

Cited by 34 publications

References 61 publications

Functional Compartmentalization of HSP60-Survivin Interaction between Mitochondria and Cytosol in Cancer Cells

Functional Compartmentalization of HSP60-Survivin Interaction between Mitochondria and Cytosol in Cancer Cells

Curcumin’s Beneficial Effects on Neuroblastoma: Mechanisms, Challenges, and Potential Solutions

Molecular mechanisms in chaperonopathies: clues to understanding the histopathological abnormalities and developing novel therapies

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