المؤلفون: Molli, Poonam R., Li, Da-Qiang, Bagheri-Yarmand, Rozita, Pakala, Suresh B., Katayama, Hiroshi, Sen, Subrata, Iyer, Jyoti, Chernoff, Jonathan, Tsai, Ming-Ying, Nair, Sujit S., Kumar, Rakesh

المصدر: The Journal of Cell Biology, 2010 Jul 01. 190(1), 101-114.

الوصول الحر: https://www.jstor.org/stable/27822131Test

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]

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المؤلفون: Pakala, Suresh B.¹, Nair, Vasudha S.¹, DivijendraNatha Reddy, Sirigiri¹, Kumar, Rakesh¹ bcmrxk@gwu.edu

المصدر: Journal of Biological Chemistry. 11/23/2012, Vol. 287 Issue 48, p40560-40569. 10p.

مصطلحات موضوعية: *PHOSPHORYLATION, *CELL cycle, *CENTROMERE, *KINESIN, *MICROTUBULES, *POLYMERIZATION, *P21 gene, *KINASES

مستخلص: Although p21-activated kinase 1 (PAK1) and microtubule (MT) dynamics regulate numerous fundamental processes including cytoskeleton remodeling, directional motility, and mitotic functions, the significance of PAK1 signaling in regulating the functions of MT-destabilizing protein mitotic centromere- associated kinesin (MCAK) remains unknown. Here we found thatMCAKis a cognate substrate of PAK1 wherein PAK1 phosphorylates MCAK on serines 192 and 111 both in vivo and in vitro. Furthermore, we found that PAK1 phosphorylation of MCAKon serines 192 and 111 preferentially regulates its microtubule depolymerization activity and localization to centrosomes, respectively, in the mammalian cells. [ABSTRACT FROM AUTHOR]