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p90 ribosomal S6 kinase 1 (RSK1) isoenzyme specifically regulates cytokinesis progression.
Cell Signal. 2014 Feb; 26(2):208-19.CS

Abstract

The p90 ribosomal S6 kinase family (RSK1-4) of Ser/Thr kinases is a downstream component of the Ras-MAPK cascade responsible for regulating various cellular processes. Here, we examined the potential involvement of RSKs in regulating mitosis by transfecting HeLa cells with siRNAs targeting RSK1 and -2, which are the major isoforms. Depletion of RSK1 but not RSK2 triggered a significant accumulation of binucleated cells compared to control cells (0.5% vs. 10.5%, respectively); this was rescued by expression of exogenous RSK1 but not a kinase-defective mutant. Monitoring of cell division by time-lapse imaging revealed that the observed binucleation mainly stemmed from a failure to form and ingress the cleavage furrow during early cytokinesis. Immunocytochemical analysis of RhoA and anillin, the two principal regulators of cleavage furrow formation and ingression, showed that these proteins were abnormally localized during anaphase in RSK1-depleted cells. Furthermore, RSK1-depleted cells seemed to have impairments in midzone microtubule formation, as suggested by morphological changes and lengthening of the midzone (15.2 ± 1.7 μm vs. 17.4 ± 1.7 μm in control cells). We also observed shortening of the pole-to-polar-cortex distance in RSK1-depleted cells (4.30 ± 1.37 μm vs. 2.80 ± 0.84 μm in control cells) and scanty distribution of microtubules at the periphery of the equatorial region during anaphase, suggesting an aberrant distribution of astral microtubules. Taken together, these results suggest that RSK1 is specifically required for cleavage furrow formation and ingression during cytokinesis. This may occur via the involvement of RSK1 in proper midzone and astral microtubule structure formation during anaphase, which is essential for the correct localization of anillin and RhoA.

Authors+Show Affiliations

Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon 443-721, Republic of Korea.Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon 443-721, Republic of Korea.Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon 443-721, Republic of Korea.Department of Molecular Cell Biology and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, Republic of Korea.Department of Biochemistry, College of Medicine, Dankook University, Chonan 330-714, Republic of Korea.Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon 443-721, Republic of Korea. Electronic address: jhlee64@ajou.ac.kr.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24269382

Citation

Nam, Hyun-Ja, et al. "P90 Ribosomal S6 Kinase 1 (RSK1) Isoenzyme Specifically Regulates Cytokinesis Progression." Cellular Signalling, vol. 26, no. 2, 2014, pp. 208-19.
Nam HJ, Lee IJ, Jang S, et al. P90 ribosomal S6 kinase 1 (RSK1) isoenzyme specifically regulates cytokinesis progression. Cell Signal. 2014;26(2):208-19.
Nam, H. J., Lee, I. J., Jang, S., Bae, C. D., Kwak, S. J., & Lee, J. H. (2014). P90 ribosomal S6 kinase 1 (RSK1) isoenzyme specifically regulates cytokinesis progression. Cellular Signalling, 26(2), 208-19. https://doi.org/10.1016/j.cellsig.2013.11.014
Nam HJ, et al. P90 Ribosomal S6 Kinase 1 (RSK1) Isoenzyme Specifically Regulates Cytokinesis Progression. Cell Signal. 2014;26(2):208-19. PubMed PMID: 24269382.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - p90 ribosomal S6 kinase 1 (RSK1) isoenzyme specifically regulates cytokinesis progression. AU - Nam,Hyun-Ja, AU - Lee,In Jeong, AU - Jang,Seunghoon, AU - Bae,Chang-Dae, AU - Kwak,Sahng-June, AU - Lee,Jae-Ho, Y1 - 2013/11/19/ PY - 2013/10/21/received PY - 2013/11/08/revised PY - 2013/11/14/accepted PY - 2013/11/26/entrez PY - 2013/11/26/pubmed PY - 2014/8/19/medline KW - Astral microtubule KW - Cleavage furrow KW - Cytokinesis KW - ERK KW - MAPK KW - MAPK/ERK kinase KW - MEK KW - MTs KW - RSK1 KW - RSKs KW - Spindle midzone KW - extracellular-signal-regulated kinase KW - microtubules KW - mitogen-activated protein kinase KW - p90 ribosomal S6 kinases KW - siRNA KW - small interfering RNA SP - 208 EP - 19 JF - Cellular signalling JO - Cell. Signal. VL - 26 IS - 2 N2 - The p90 ribosomal S6 kinase family (RSK1-4) of Ser/Thr kinases is a downstream component of the Ras-MAPK cascade responsible for regulating various cellular processes. Here, we examined the potential involvement of RSKs in regulating mitosis by transfecting HeLa cells with siRNAs targeting RSK1 and -2, which are the major isoforms. Depletion of RSK1 but not RSK2 triggered a significant accumulation of binucleated cells compared to control cells (0.5% vs. 10.5%, respectively); this was rescued by expression of exogenous RSK1 but not a kinase-defective mutant. Monitoring of cell division by time-lapse imaging revealed that the observed binucleation mainly stemmed from a failure to form and ingress the cleavage furrow during early cytokinesis. Immunocytochemical analysis of RhoA and anillin, the two principal regulators of cleavage furrow formation and ingression, showed that these proteins were abnormally localized during anaphase in RSK1-depleted cells. Furthermore, RSK1-depleted cells seemed to have impairments in midzone microtubule formation, as suggested by morphological changes and lengthening of the midzone (15.2 ± 1.7 μm vs. 17.4 ± 1.7 μm in control cells). We also observed shortening of the pole-to-polar-cortex distance in RSK1-depleted cells (4.30 ± 1.37 μm vs. 2.80 ± 0.84 μm in control cells) and scanty distribution of microtubules at the periphery of the equatorial region during anaphase, suggesting an aberrant distribution of astral microtubules. Taken together, these results suggest that RSK1 is specifically required for cleavage furrow formation and ingression during cytokinesis. This may occur via the involvement of RSK1 in proper midzone and astral microtubule structure formation during anaphase, which is essential for the correct localization of anillin and RhoA. SN - 1873-3913 UR - https://www.unboundmedicine.com/medline/citation/24269382/p90_ribosomal_S6_kinase_1__RSK1__isoenzyme_specifically_regulates_cytokinesis_progression_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0898-6568(13)00345-8 DB - PRIME DP - Unbound Medicine ER -