Copine1 C2 domains have a critical calcium-independent role in the neuronal differentiation of hippocampal progenitor HiB5 cells

Park, Nammi; Yoo, Jae Cheal; Choi, Hye Young; Hong, Seong Geun; Hwang, Eun Mi; Park, Jae Yong

doi:10.1016/j.bbrc.2014.10.075

Cited by 27 publications

(31 citation statements)

References 18 publications

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“…It has shown that the PI3K/AKT signaling pathway mediates multiple cellular processes, including cell differentiation, apoptosis, and viability. CPNE1 can directly induce the differentiation of hippocampal progenitor cells via AKT phosphorylation 15 . Inhibiting PI3K/Akt signaling pathway resulted in decreased cell proliferation and increased cell apoptosis in TNBC 21,22 .…”

Section: Discussionmentioning

confidence: 96%

“…CPNE1 is a recently discovered calcium‐dependent membrane‐binding protein with a broad tissue distribution and may regulate signal transduction and membrane trafficking. Dysregulation of CPNE1 is related to various pathologies such as osteoarthritis, neuronal disorders, and tumorigenesis 9‐12,15,20 . However, its role in TNBC tumorigenesis and radioresistance is not understood.…”

Section: Discussionmentioning

confidence: 99%

“…AKT pathway has been found to be associated with various cellular functions, including cell survival, motility, cell cycle progression, chemoresistance, and radioresistance 13,14 . CPNE1 can directly induce the differentiation of hippocampal progenitor cells via AKT phosphorylation 15 . However, whether CPNE1 can regulate tumorigenesis and radiosensitivity in TNBC is not well understood.…”

Section: Introductionmentioning

confidence: 99%

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CPNE1 predicts poor prognosis and promotes tumorigenesis and radioresistance via the AKT singling pathway in triple‐negative breast cancer

Shao

Zhang³

et al. 2020

Molecular Carcinogenesis

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Elevated expression of Copine 1 (CPNE1) has been observed in multiple cancers; however, the underlying mechanisms by which it affects cancer cells are unclear. We aimed to study the effect of CPNE1 on the tumorigenesis and radioresistance of triple‐negative breast cancer (TNBC). Quantitative real‐time polymerase chain reaction was used to detect the expression of CPNE1 in TNBC tissues and cell lines. Western blot, immunohistochemistry, and immunofluorescence were used to investigate the levels of CPNE1, p‐AKT, AKT, cleaved caspase‐3, cleaved PARP1, and γ‐H2AX. Cell viability and apoptosis were measured by CCK‐8 and flow cytometry, respectively. CPNE1 was overexpressed in TNBC tissues and cell lines and was associated with tumor size, distant metastases, and survival rates of patients with TNBC. Moreover, function study shows that CPNE1 promoted cell viability and inhibited cell apoptosis in vitro and inhibited the radiosensitivity of TNBC. Importantly, inactivation of AKT signaling inhibited the tumorigenesis and radioresistance mediated by CPNE1 in TNBC cells. In vivo xenograft study also shows that CPNE1 knockdown inhibited tumor growth and promoted cell apoptosis. Overall, our findings suggest that CPNE1 promotes tumorigenesis and radioresistance in TNBC by regulating AKT activation and targeted CPNE1 expression may be a strategy to sensitize TNBC cells toward radiation therapy.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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CPNE1 predicts poor prognosis and promotes tumorigenesis and radioresistance via the AKT singling pathway in triple‐negative breast cancer

Shao

Zhang³

et al. 2020

Molecular Carcinogenesis

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“…Together, these results strongly suggest that the C2B‐domains of the three copines are responsible for their calcium sensitivity and their membrane attachment, although Parks et al . have reported that the native C2A‐domain of human copine‐1 is sufficient to maintain the protein calcium‐dependent membrane binding if the C2B‐domain is mutated to disrupt its calcium‐binding ability .…”

Section: Discussionmentioning

confidence: 99%

The second C2‐domain of copine‐2, copine‐6 and copine‐7 is responsible for their calcium‐dependent membrane association

et al. 2015

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The copine family of proteins contains nine members with a similar domain structure, namely two N‐terminal C2‐domains (C2A and C2B) and a C‐terminal A‐domain. The former are thought to be responsible for binding to the inner face of the plasma membrane following increases in intracellular calcium levels, whereas the A‐domain has been suggested to be a protein‐binding structure. In this study, we examined the effects of mutagenesis of selected residues in the linker area between the C2‐domains and the A‐domain, and mutagenesis of the aspartates of the C2‐domains, which are predicted to bind calcium and promote membrane association of the copines. We found that Lys282–Lys284 of the linker area are important for the folding of the intact protein. We showed that substitution with asparagine, single or multiple, of the aspartates in the C2A‐domain had no effect on the calcium‐mediated membrane association of copine‐2, copine‐6, or copine‐7. Similar mutagenesis of a single residue in the C2B‐domain of copine‐6 (but not copine‐2 and copine‐7) was sufficient to eliminate its calcium‐mediated membrane binding, and simultaneous substitution of all four of the asparagines in the C2B‐domain resulted in constitutive membrane association of copine‐2, copine‐6 and copine‐7 with the plasma membrane. These data show that the C2B‐domains of copine‐2, copine‐6 and copine‐7 are the domains responsible for the protein calcium‐dependent membrane association.

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“…Although our transcriptional analysis of skin punch biopsies only produced 4 significant transcripts, 2 of these are of interest in relation to AD: ISG15 has been proposed as a general marker of acute and chronic neuronal injury [24] and alterations in LDLR has been identified in association and AD in humans [25] as well as animal models of AD [26]. The most significant transcript identified from punch biopsies, CPNE1 (Copine-1), has not been described in neurodegenerative disorders; however, it has been suggested to play an important role in neuronal differentiation [27]. …”

Section: Discussionmentioning

confidence: 99%

Transcriptional Analysis of Blood Lymphocytes and Skin Fibroblasts, Keratinocytes, and Endothelial Cells as a Potential Biomarker for Alzheimer’s Disease

Mukhamedyarov

Rizvanov

Yakupov

et al. 2016

JAD

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Alzheimer’s disease (AD) is a devastating and progressive form of dementia that is typically associated with a build-up of amyloid-β plaques and hyperphosphorylated and misfolded tau protein in the brain. Presently, there is no single test that confirms AD; therefore, a definitive diagnosis is only made after a comprehensive medical evaluation, which includes medical history, cognitive tests, and a neurological examination and/or brain imaging. Additionally, the protracted prodromal phase of the disease makes selection of control subjects for clinical trials challenging. In this study we have utilized a gene-expression array to screen blood and skin punch biopsy (fibroblasts, keratinocytes, and endothelial cells) for transcriptional differences that may lead to a greater understanding of AD as well as identify potential biomarkers. Our analysis identified 129 differentially expressed genes from blood of dementia cases when compared to healthy individuals, and four differentially expressed punch biopsy genes between AD subjects and controls. Additionally, we identified a set of genes in both tissue compartments that showed transcriptional variation in AD but were largely stable in controls. The translational products of these variable genes are involved in the maintenance of the Golgi structure, regulation of lipid metabolism, DNA repair, and chromatin remodeling. Our analysis potentially identifies specific genes in both tissue compartments that may ultimately lead to useful biomarkers and may provide new insight into the pathophysiology of AD.

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Copine1 C2 domains have a critical calcium-independent role in the neuronal differentiation of hippocampal progenitor HiB5 cells

Cited by 27 publications

References 18 publications

CPNE1 predicts poor prognosis and promotes tumorigenesis and radioresistance via the AKT singling pathway in triple‐negative breast cancer

CPNE1 predicts poor prognosis and promotes tumorigenesis and radioresistance via the AKT singling pathway in triple‐negative breast cancer

The second C2‐domain of copine‐2, copine‐6 and copine‐7 is responsible for their calcium‐dependent membrane association

Transcriptional Analysis of Blood Lymphocytes and Skin Fibroblasts, Keratinocytes, and Endothelial Cells as a Potential Biomarker for Alzheimer’s Disease

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