المؤلفون: Guddeti, Rohith Kumar, Thomas, Liz, Kannan, Anbarasu, Karyala, Prashanthi, Pakala, Suresh B., Nebreda, Angel

المصدر: FEBS Letters; May2021, Vol. 595 Issue 9, p1289-1302, 14p

مصطلحات موضوعية: GLUCOSE metabolism, LACTATE dehydrogenase, ZINC-finger proteins, CANCER cell migration, CHROMATIN, ENZYME metabolism, GENE targeting

مستخلص: Microrchidia family CW‐type zinc finger 2 (MORC2) is a recently identified chromatin modifier with an emerging role in cancer metastasis. However, its role in glucose metabolism, a hallmark of malignancy, remains to be explored. We found that MORC2 is a glucose‐inducible gene and a target of c‐Myc. Our meta‐analysis revealed that MORC2 expression is positively correlated with the expression of enzymes involved in glucose metabolism in breast cancer patients. Furthermore, overexpression of MORC2 in MCF‐7 and BT‐549 cells augmented the expression and activity of a key glucose metabolism enzyme, lactate dehydrogenase A (LDHA). Conversely, selective knockdown of MORC2 by siRNA markedly decreased LDHA expression and activity and in turn reduced cancer cell migration. Collectively, these findings provide evidence that MORC2, a glucose‐inducible gene, modulates the migration of breast cancer cells through the MORC2–c‐Myc–LDHA axis. [ABSTRACT FROM AUTHOR]

: Copyright of FEBS Letters is the property of Wiley-Blackwell 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: Li, Da-Qiang, Nair, Sujit S., Ohshiro, Kazufumi, Kumar, Anupam, Nair, Vasudha S., Pakala, Suresh B., Reddy, Sirigiri Divijendra Natha, Gajula, Rajendra P., Eswaran, Jeyanthy, Aravind, L., Kumar, Rakesh

المصدر: Cell Reports; Dec2012, Vol. 2 Issue 6, p1657-1669, 13p

مصطلحات موضوعية: ZINC-finger proteins, CELLULAR signal transduction, PHOSPHORYLATION, ADENOSINE triphosphatase, CHROMATIN, DNA damage

مستخلص: Summary: Chromatin dynamics play a central role in maintaining genome integrity, but how this is achieved remains largely unknown. Here, we report that microrchidia CW-type zinc finger 2 (MORC2), an uncharacterized protein with a derived PHD finger domain and a conserved GHKL-type ATPase module, is a physiological substrate of p21-activated kinase 1 (PAK1), an important integrator of extracellular signals and nuclear processes. Following DNA damage, MORC2 is phosphorylated on serine 739 in a PAK1-dependent manner, and phosphorylated MORC2 regulates its DNA-dependent ATPase activity to facilitate chromatin remodeling. Moreover, MORC2 associates with chromatin and promotes gamma-H2AX induction in a PAK1 phosphorylation-dependent manner. Consequently, cells expressing MORC2-S739A mutation displayed a reduction in DNA repair efficiency and were hypersensitive to DNA-damaging agent. These findings suggest that the PAK1-MORC2 axis is critical for orchestrating the interplay between chromatin dynamics and the maintenance of genomic integrity through sequentially integrating multiple essential enzymatic processes. [Copyright &y& Elsevier]

: Copyright of Cell Reports is the property of Elsevier B.V. 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.)