Редактирование: CARF

Calcium-responsive transcription factor (Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 8 protein) (Calcium-response factor) (CaRF) (Testis development protein NYD-SP24) [ALS2CR8]

==Publications==

{{medline-entry
|title=Induction of Senescence in Cancer Cells by a Novel Combination of Cucurbitacin B and Withanone: Molecular Mechanism and Therapeutic Potential.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31112603
|abstract=Cancer, an uncontrolled proliferation syndrome, is treated with synthetic chemotherapeutic drugs that are associated with severe adverse effects. Development and application of new natural compounds is warranted to deal with the exponentially increasing incidence of cancer worldwide. Keeping selective toxicity to cancer cells as a priority criterion, we developed a combination of Cucurbitacin B and Withanone, and analyzed its anticancer potential using non-small cell lung cancer cells. We demonstrate that the selective cytotoxicity of the combination, called CucWi-N, to cancer cells is mediated by induction of cellular senescence that was characterized by decrease in Lamin A/C, [[CDK2]], [[CDK4]], Cyclin D, Cyclin E, phosphorylated RB, mortalin and increase in p53 and [[CARF]] proteins. It compromised cancer cell migration that was mediated by decrease in mortalin, hnRNP-K, vascular endothelial growth factor, matrix metalloproteinase 2, and fibronectin. We provide in silico, molecular dynamics and experimental data to support that CucWi-N (i) possesses high capability to target mortalin-p53 interaction and hnRNP-K proteins, (ii) triggers replicative senescence and inhibits metastatic potential of the cancer cells, and (iii) inhibits tumor progression and metastasis in vivo. We propose that CucWi-N is a potential natural anticancer drug that warrants further mechanistic and clinical studies.

|keywords=* Anticancer
* Antimetastatic
* Cucurbitacin B
* Senescence
* Withanone
|full-text-url=https://sci-hub.do/10.1093/gerona/glz077
}}
{{medline-entry
|title=[[CARF]] is a multi-module regulator of cell proliferation and a molecular bridge between cellular senescence and carcinogenesis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28754531
|abstract=[[CARF]] (Collaborator of ARF) was first identified as an ARF (Alternative Reading Frame, p14ARF)-interacting protein in a yeast two-hybrid interactive screening. Subsequently, it was shown to stabilize the p53-tumor suppressor protein in an ARF-dependent or -independent manner. It acts as a transcriptional repressor of HDM2 that exerts a negative feedback on p53 by its proteasomal-mediated degradation. [[CARF]]-driven control over p53-HDM2-p21  axis was shown to regulate cell proliferative fates. Cells with [[CARF]]-overexpression ([[CARF]]-OE) and superexpression ([[CARF]]-SE) showed growth arrest and pro-proliferative phenotypes, respectively. On the other hand, apoptosis was triggered in [[CARF]]-compromised cells. In the present review, we provide a comprehensive current understanding into the molecular mechanisms of [[CARF]] functions in regulation of DNA damage response, cell cycle checkpoints, cell survival and death signaling pathways. We discuss how thresh-hold of [[CARF]] level determines fate of cells to senescence and malignant transformation.
|mesh-terms=* Animals
* Apoptosis Regulatory Proteins
* Cell Cycle Checkpoints
* Cell Transformation, Neoplastic
* Cellular Senescence
* Cyclin-Dependent Kinase Inhibitor p21
* DNA Damage
* Humans
* Proto-Oncogene Proteins c-mdm2
* RNA-Binding Proteins
* Tumor Suppressor Protein p14ARF
* Tumor Suppressor Protein p53
|keywords=* CARF
* Malignant transformation
* Overexpression
* Senescence
* Superexpression
|full-text-url=https://sci-hub.do/10.1016/j.mad.2017.07.008
}}
{{medline-entry
|title=Collaborator of ARF ([[CARF]]) regulates proliferative fate of human cells by dose-dependent regulation of DNA damage signaling.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24825908
|abstract=Collaborator of ARF ([[CARF]]) has been shown to directly bind to and regulate p53, a central protein that controls tumor suppression via cellular senescence and apoptosis. However, the cellular functions of [[CARF]] and the mechanisms governing its effect on senescence, apoptosis, or proliferation are still unknown. Our previous studies have shown that (i) [[CARF]] is up-regulated during replicative and stress-induced senescence, and its exogenous overexpression caused senescence-like growth arrest of cells, and (ii) suppression of [[CARF]] induces aneuploidy, DNA damage, and mitotic catastrophe, resulting in apoptosis via the ATR/CHK1 pathway. In the present study, we dissected the cellular role of [[CARF]] by investigating the molecular pathways triggered by its overexpression in vitro and in vivo. We found that the dosage of [[CARF]] is a critical factor in determining the proliferation potential of cancer cells. Most surprisingly, although a moderate level of [[CARF]] overexpression induced senescence, a very high level of [[CARF]] resulted in increased cell proliferation. We demonstrate that the level of [[CARF]] is crucial for DNA damage and checkpoint response of cells through ATM/CHK1/CHK2, p53, and ERK pathways that in turn determine the proliferative fate of cancer cells toward growth arrest or proproliferative and malignant phenotypes. To the best of our knowledge, this is the first report that demonstrates the capability of a fundamental protein, [[CARF]], in controlling cell proliferation in two opposite directions and hence may play a key role in tumor biology and cancer therapeutics. 
|mesh-terms=* Apoptosis
* Apoptosis Regulatory Proteins
* Ataxia Telangiectasia Mutated Proteins
* Cell Line, Tumor
* Cell Proliferation
* DNA Damage
* Humans
* Neoplasms
* RNA-Binding Proteins
* Signal Transduction
* Tumor Suppressor Protein p53
|keywords=* CARF
* Cell Proliferation
* Cellular Regulation
* Cellular Senescence
* DNA Damage Response
* Malignant
* p53
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4140265
}}
{{medline-entry
|title=Molecular characterization of collaborator of ARF ([[CARF]]) as a DNA damage response and cell cycle checkpoint regulatory protein.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24485912
|abstract=[[CARF]] is an ARF-binding protein that has been shown to regulate the p53-p21-HDM2 pathway. [[CARF]] overexpression was shown to cause growth arrest of human cancer cells and premature senescence of normal cells through activation of the p53 pathway. Because replicative senescence involves permanent withdrawal from the cell cycle in response to DNA damage response-mediated signaling, in the present study we investigated the relationship between [[CARF]] and the cell cycle and whether it is involved in the DNA damage response. We demonstrate that the half-life of [[CARF]] protein is less than 60 min, and that in cycling cells [[CARF]] levels are highest in G2 and early prophase. Serially passaged normal human skin and stromal fibroblasts showed upregulation of [[CARF]] during replicative senescence. Induction of G1 growth arrest and senescence by a variety of drugs was associated with increase in [[CARF]] expression at the transcriptional and translational level and was seen to correlate with increase in DNA damage response and checkpoint proteins, [[ATM]], [[ATR]], CHK1, CHK2, γH2AX, p53 and p21. Induction of growth arrest by oncogenic RAS and shRNA-mediated knockdown of TRF2 in cancer cells also caused upregulation of [[CARF]]. We conclude that [[CARF]] is associated with DNA damage response and checkpoint signaling pathways.
|mesh-terms=* Antineoplastic Agents
* Apoptosis
* Apoptosis Regulatory Proteins
* Blotting, Western
* Cell Cycle Checkpoints
* Cell Cycle Proteins
* Cell Proliferation
* Cells, Cultured
* Cellular Senescence
* DNA Damage
* Fibroblasts
* Fluorescent Antibody Technique
* Humans
* Neoplasms
* Promoter Regions, Genetic
* RNA, Messenger
* RNA, Small Interfering
* RNA-Binding Proteins
* Real-Time Polymerase Chain Reaction
* Reverse Transcriptase Polymerase Chain Reaction
* Skin
* Stromal Cells
* Telomeric Repeat Binding Protein 2
|keywords=* CARF
* DNA damage response
* Mechanism
* Senescence
* Upregulation
|full-text-url=https://sci-hub.do/10.1016/j.yexcr.2014.01.022
}}