Since apoptosis presents a natural defense in cancer development, the anti-apoptotic factor AATF/Che-1 has emerged as a crucial 'Epigenomic-Switch'. We have tried to understand the double-edged nature of AATF, showing for the first time the conspicuous existence of an aberrant AATF/Che-1 transcriptome encoding for 23 kDa mutant AATF protein, which evolves its unique interactome within human cancer cells derived from different tissue origins. This mutant AATF along with its interactome consisting of SP1, DNMT3B and Par-4 ensures cancer cell DNA methylation required for down-regulation of tumor suppressor genes. Hence, the proposed mutant AATF interactome-based pathway can have the inherent ability to ensure human cells become and remain cancerous.
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CK2-mediated phosphorylation of Che-1/AATF is required for its pro-proliferative activity.
J Exp Clin Cancer Res
July 2021
SAFU Laboratory, Department of Research, Advanced Diagnostics and Technological Innovation, Translational Research Area, IRCCS Regina Elena National Cancer Institute, Via E. Chianesi 53, 00144, Rome, Italy.
Background: Che-1/AATF (Che-1) is an RNA polymerase II binding protein involved in several cellular processes, including proliferation, apoptosis and response to stress. We have recently demonstrated that Che-1 is able to promote cell proliferation by sustaining global histone acetylation in multiple myeloma (MM) cells where it interacts with histone proteins and competes with HDAC class I members for binding.
Methods: Site-directed Mutagenesis was performed to generate a Che-1 mutant (Che-1 3S) lacking three serine residues (Ser, Ser and Ser) in 308-325 aa region.
APOBEC3G governs the generation of truncated AATF protein to ensure oncogenic transformation.
Cell Biol Int
December 2016
Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.
The oncogenic potential of Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3G (APOBEC3G) was recently appreciated by the finding that revealed its ability to downregulate Kruppel-like factor 4 (KLF4) gene translation through its affinity for 3'UTR of KLF4 mRNA. Keeping in view the fact that KLF4 is known to repress apoptosis antagonizing transcription factor (AATF) gene expression, the present study employed stem cells as archetype model to explore the effect of APOBEC3G over-expression upon AATF gene expression within these cells as well as on the genes involved in oncogenic transformation. Such a study revealed that APOBEC3G had the ability to bind AATF mRNA within its third exon to facilitate the generation of truncated 23 kDa AATF translation product which, in turn, had the inherent capacity to be the crucial mediator of APOBEC3G induced oncogenic transformation within such cells.
View Article and Find Full Text PDFChe-1 gene silencing induces osteosarcoma cell apoptosis by inhibiting mutant p53 expression.
Biochem Biophys Res Commun
April 2016
Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou 450052, Henan, China.
The transcriptional cofactor Che-1 is an RNA polymerase II (Pol II) which is involved in tumorigenesis, such as breast cancer and multiple myeloma. Che-1 can also regulate mutant p53 expression, which plays roles in many types of cancer. In this study, we aimed to investigate the effects and specific mechanism of Che-1 in the regulation of osteosarcoma (OS) cell growth.
View Article and Find Full Text PDFChe-1/AATF: A Critical Cofactor for Both Wild-Type- and Mutant-p53 Proteins.
Front Oncol
February 2016
SAFU Laboratory, Department of Research, Advanced Diagnostic, and Technological Innovation, Regina Elena Cancer Institute, Rome , Italy.
The p53 protein is a key player in a wide range of protein networks that allow the state of "good health" of the cell. Not surprisingly, mutations of the TP53 gene are one of the most common alterations associated to cancer cells. Mutated forms of p53 (mtp53) not only lose the ability to protect the integrity of the genetic heritage of the cell but also acquire pro-oncogenic functions, behaving like dangerous accelerators of transformation and tumor progression.
View Article and Find Full Text PDFOncogenic nature of a novel mutant AATF and its interactome existing within human cancer cells.
Cell Biol Int
March 2015
Department of Experimental Medicine & Biotechnology, Molecular Biology Unit, Post-graduate Institute of Medical Education & Research, Chandigarh, 160012, India.
Since apoptosis presents a natural defense in cancer development, the anti-apoptotic factor AATF/Che-1 has emerged as a crucial 'Epigenomic-Switch'. We have tried to understand the double-edged nature of AATF, showing for the first time the conspicuous existence of an aberrant AATF/Che-1 transcriptome encoding for 23 kDa mutant AATF protein, which evolves its unique interactome within human cancer cells derived from different tissue origins. This mutant AATF along with its interactome consisting of SP1, DNMT3B and Par-4 ensures cancer cell DNA methylation required for down-regulation of tumor suppressor genes.
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