Overexpression of ErbB2 renders breast cancer cells susceptible to 3-BrPA through the increased dissociation of hexokinase II from mitochondrial outer membrane

Gao, Sujie; Chen, Xuebo; Jin, Hao; Ren, Shengnan; Liu, Zhuo; Fang, Xuedong; Zhang, Guizhen

doi:10.3892/ol.2015.4043

Cited by 13 publications

(8 citation statements)

References 22 publications

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“…Protein structural analysis showed that this mutation was located in the P region (phosphorylation In keratinocytes, hSPCA1 not only transports Ca 2+ , but also competitively transports one Mn 2+ from the cytoplasm to the Golgi apparatus, which is nonreplaceable by other calcium pumps. It is known that the cells are very sensitive to Mn 2+ concentration and a slight change of Mn 2+ concentration may affect cell metabolism seriously [16]. Excessive intracellular Mn 2+ may prevent Mg 2+ binding to proteins, compromise the fidelity of DNA polymerase, and disrupt the transport function of cell membranes, thus affecting the physiological conditions of human body [17,18].…”

Section: Discussionmentioning

confidence: 99%

Identification of ATP2C1 mutations in the patients of Hailey-Hailey disease

Zhang

Ding

et al. 2020

BMC Med Genet

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Background: Familial benign chronic pemphigus, also known as Hailey-Hailey disease (HHD), is a clinically rare bullous Dermatosis. However the mechanism has not been clarified. The study aim to detect novel mutations in exons of ATP2C1 gene in HHD patients; to explore the possible mechnism of HHD pathogenesis by examining the expression profile of hSPCA1, miR-203, p63, Notch1 and HKII proteins in the skin lesions of HHD patients. Methods: Genomic DNA was extracted from peripheral blood of HHD patients. All exons of ATP2C1 gene in HHD patients were amplified by PCR and the products were purified and sequenced. All related signaling proteins of interest were stained by using skin lesion tissues from HHD patients and miR-203 levels were also determined. Results: One synonymous mutation c.G2598A (in exon 26), one nonsense mutation c.C635A and two missense mutations c.C1286A (p.A429D) and c. A1931G (p. D644G) were identified. The nonsense mutation changed codon UCG to stop codon UAG, causing a premature polypeptide chain of the functional region A. The two missense mutations were located in the region P (phosphorylation region) and the Mn binding site of hSPCA1. The level of hSPCA1 was significantly decreased in HHD patients compared to the normal human controls, accompanied by an increase of miR-203 level and a decrease of p63 and HKII levels. Conclusion: In our study, we found four mutations in HHD. Meanwhile we found increase of miR-203 level and a decrease of p63 and HKII levels. In addition, Notch1, which was negatively regulated p63, is downregulated. These factors may be involved in the signaling pathways of HHD pathogenesis. Our data showed that both p63 and miR-203 may have significant regulatory effects on Notch1 in the skin.

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Section: Discussionmentioning

confidence: 99%

Identification of ATP2C1 mutations in the patients of Hailey-Hailey disease

Zhang

Ding

et al. 2020

BMC Med Genet

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“…We found that the ErbB2 signaling is a critical pathway involved in PD, which was in line with the reported studies. 43,74,75 Accordingly, western blot results showed that ErbB2 pY-1248 protein expression was dramatically upregulated in the cellular PD model. In contrast, there was no apparent change in the protein expression of ErbB1 and ErbB2.…”

Section: Discussionmentioning

confidence: 99%

ErbB2_pY_‐1248 as a predictive biomarker for Parkinson's disease based on research with RPPA technology and in vivo verification

et al. 2023

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AimsThis study aims to reveal a promising biomarker for Parkinson's disease (PD) based on research with reverse phase protein array (RPPA) technology for the first time and in vivo verification, which gains time for early intervention in PD, thus increasing the effectiveness of treatment and reducing disease morbidity.Methods and ResultsWe employed RPPA technology which can assess both total and post‐translationally modified proteins to identify biomarker candidates of PD in a cellular PD model. As a result, the phosphorylation (pY‐1248) of the epidermal growth factor receptor (EGFR) ErbB2 is a promising biomarker candidate for PD. In addition, lapatinib, an ErbB2 tyrosine kinase inhibitor, was used to verify this PD biomarker candidate in vivo. We found that lapatinib‐attenuated dopaminergic neuron loss and PD‐like behavior in the zebrafish PD model. Accordingly, the expression of ErbB2pY‐1248 significantly increased in the MPTP‐induced mouse PD model. Our results suggest that ErbB2pY‐1248 is a predictive biomarker for PD.ConclusionsIn this study, we found that ErbB2pY‐1248 is a predictive biomarker of PD by using RPPA technology and in vivo verification. It offers a new perspective on PD diagnosing and treatment, which will be essential in identifying individuals at risk of PD. In addition, this study provides new ideas for digging into biomarkers of other neurodegenerative diseases.

show abstract

“…In keratinocytes, hSPCA1 not only transports Ca 2+ , but also competitively transports one Mn 2+ from the cytoplasm to the Golgi apparatus, which is nonreplaceable by other calcium pumps. It is known that the cells are very sensitive to Mn 2+ concentration and a slight change of Mn 2+ concentration may affect cell metabolism seriously [16]. Excessive intracellular Mn 2+ may prevent Mg 2+ binding to proteins, compromise the delity of DNA polymerase, and disrupt the transport function of cell membranes, thus affecting the physiological conditions of human body [17,18].…”

Section: Discussionmentioning

confidence: 99%

Identification of ATP2C1 mutations in the patients of Hailey-Hailey disease

zhang

ding

et al. 2020

Preprint

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Background: Familial benign chronic pemphigus, also known as Hailey-Hailey disease (HHD), is a clinically rare bullous Dermatosis. However the mechanism has not been clarified. The study aim to detect novel mutations in exons of ATP2C1 gene in HHD patients; to explore the possible mechnism of HHD pathogenesis by examining the expression profile of hSPCA1, miR-203, p63, Notch1 and HKⅡ proteins in the skin lesions of HHD patients. Methods: Genomic DNA was extracted from peripheral blood of HHD patients. All exons of ATP2C1 gene in HHD patients were amplified by PCR and the products were purified and sequenced. All related signaling proteins of interest were stained by using skin lesion tissues from HHD patients and miR-203 levels were also determined. Results: One synonymous mutation c.G2598A (in exon 26), one nonsense mutation c.C635A and two missense mutations c.C1286A (p.A429D) and c. A1931G (p. D644G) were identified. The nonsense mutation changed codon UCG to stop codon UAG, causing a premature polypeptide chain of the functional region A. The two missense mutations were located in the region P (phosphorylation region) and the Mn binding site of hSPCA1. The level of hSPCA1 was significantly decreased in HHD patients compared to the normal human controls, accompanied by an increase of miR-203 level and a decrease of p63 and HKⅡ levels. Conclusion: In our study, we found four mutations in HHD. Meanwhile we found increase of miR-203 level and a decrease of p63 and HKⅡ levels. In addition, Notch1, which was negatively regulated p63, is downregulated. These factors may be involved in the signaling pathways of HHD pathogenesis. Our data showed that both p63 and miR-203 may have significant regulatory effects on Notch1 in the skin.

show abstract

Overexpression of ErbB2 renders breast cancer cells susceptible to 3-BrPA through the increased dissociation of hexokinase II from mitochondrial outer membrane

Cited by 13 publications

References 22 publications

Identification of ATP2C1 mutations in the patients of Hailey-Hailey disease

Identification of ATP2C1 mutations in the patients of Hailey-Hailey disease

ErbB2_pY_‐1248 as a predictive biomarker for Parkinson's disease based on research with RPPA technology and in vivo verification

Identification of ATP2C1 mutations in the patients of Hailey-Hailey disease

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Overexpression of ErbB2 renders breast cancer cells susceptible to 3-BrPA through the increased dissociation of hexokinase II from mitochondrial outer membrane

Cited by 13 publications

References 22 publications

Identification of ATP2C1 mutations in the patients of Hailey-Hailey disease

Identification of ATP2C1 mutations in the patients of Hailey-Hailey disease

ErbB2pY‐1248 as a predictive biomarker for Parkinson's disease based on research with RPPA technology and in vivo verification

Identification of ATP2C1 mutations in the patients of Hailey-Hailey disease

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ErbB2_pY_‐1248 as a predictive biomarker for Parkinson's disease based on research with RPPA technology and in vivo verification