المؤلفون: Chutani, Namita, Ragula, Sandhya, Syed, Khajamohiddin, Pakala, Suresh B.

المصدر: Biomolecules (2218-273X); Oct2023, Vol. 13 Issue 10, p1527, 12p

مصطلحات موضوعية: TUMOR suppressor genes, CANCER cell growth, CANCER cell migration, CHROMATIN, ADENOSINE triphosphate, CARCINOGENS, MOLECULAR pathology, CELL migration inhibition

مستخلص: A newly discovered chromatin remodeler, MORC2, is a Microrchidia (MORC) family member. MORC2 acts as a chromatin remodeler by binding to the DNA and changing chromatin conformation using its ATPase domain. MORC2 is highly expressed in a variety of human cancers. It controls diverse signaling pathways essential for cancer development through its target genes and interacting partners. MORC2 promotes cancer cells' growth, invasion, and migration by regulating the expression of genes involved in these processes. MORC2 is localized primarily in the nucleus and is also found in the cytoplasm. In the cytoplasm, MORC2 interacts with adenosine triphosphate (ATP)-citrate lyase (ACLY) to promote lipogenesis and cholesterogenesis in cancer. In the nucleus, MORC2 interacts with the transcription factor c-Myc to control the transcription of genes involved in glucose metabolism to drive cancer cell migration and invasion. Furthermore, MORC2 recruits on to the promoters of tumor suppressor genes to repress their transcription and expression to promote oncogenesis. In addition to its crucial function in oncogenesis, it plays a vital role in DNA repair. Overall, this review concisely summarizes the current knowledge about MORC2-regulated molecular pathways involved in cancer. [ABSTRACT FROM AUTHOR]

: Copyright of Biomolecules (2218-273X) is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Guddeti, Rohith Kumar, Chutani, Namita, Pakala, Suresh B.

المصدر: Biophysical Reviews; Aug2021, Vol. 13 Issue 4, p507-514, 8p

مستخلص: Microrchidia 2 (MORC2) is an emerging chromatin modifier with a role in chromatin remodeling and epigenetic regulation. MORC2 is found to be upregulated in most cancers, playing a significant role in tumorigenesis and tumor metastasis. Recent studies have demonstrated that MORC2 is a scaffolding protein, which interacts with the proteins involved in DNA repair, chromatin remodeling, lipogenesis, and glucose metabolism. In this review, we discuss the domain architecture and cellular and subcellular localization of MORC2. Further, we highlight MORC2-specific interacting partners involved in metabolic reprogramming and other pathological functions such as cancer progression and metastasis. [ABSTRACT FROM AUTHOR]

: Copyright of Biophysical Reviews is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Ohshiro, Kazufumi, Rayala, Suresh K, Wigerup, Caroline, Pakala, Suresh B, Natha, Reddy S Divijendra, Gururaj, Anupama E, Molli, Poonam R, Månsson, Sofie Svensson, Ramezani, Ali, Hawley, Robert G, Landberg, Göran, 1963, Lee, Norman H, Kumar, Rakesh

المصدر: EMBO reports. 11(9):691-7

مصطلحات موضوعية: Cell and Molecular Biology, Cell- och molekylärbiologi, Acetylation, Animals, Cell Line, Cell Movement, Cell Transformation, Neoplastic, Female, Fibroblasts, cytology, physiology, GTP-Binding Protein alpha Subunit, Gi2, genetics, metabolism, Gene Expression Regulation, Histone Deacetylases, Humans, Lysine, Mice, Nude, Neoplasms, Experimental, Oncogenes, Repressor Proteins, Transcription, Genetic, Transplantation, Heterologous, ras Proteins

الوصف: High expression of metastasis-associated protein 1 co-regulator (MTA1), a component of the nuclear remodelling and histone deacetylase complex, has been associated with human tumours. However, the precise role of MTA1 in tumorigenesis remains unknown. In this study, we show that induced levels of MTA1 are sufficient to transform Rat1 fibroblasts and that the transforming potential of MTA1 is dependent on its acetylation at Lys626. Underlying mechanisms of MTA1-mediated transformation include activation of the Ras-Raf pathway by MTA1 but not by acetylation-inactive MTA1; this was due to the repression of Galphai2 transcription, which negatively influences Ras activation. We observed that acetylated MTA1-histone deacetylase (HDAC) interaction was required for the recruitment of the MTA1-HDAC complex to the Galphai2 regulatory element and consequently for the repression of Galphai2 transcription and expression leading to activation of the Ras-Raf pathway. The findings presented in this study provide for the first time--to the best of our knowledge--evidence of acetylation-dependent oncogenic activity of a cancer-relevant gene product.

الوصول الحر: https://gup.ub.gu.se/publication/150800Test