We speculate that p38 activity promotes timely checkpoint satisfaction by indirectly influencing those electric motor protein (e.g., Klp10, Klp67A) involved with regulating the dynamics of kinetochore microtubule ends. INTRODUCTION p38, an associate from the mitogen-activated proteins kinase (MAPK) family, mediates a significant cell cycle checkpoint control pathway that guards entrance into mitosis (we.e., the G2/M changeover). index. Nevertheless, under this problem chromatid cytokinesis and segregation are regular. Using Mad2/YFP-expressing cells, we present the prolongation of mitosis in the lack of p38 activity is normally directly because of a hold off in fulfilling the mitotic checkpoint. Inhibiting p38 didn’t affect the price of chromosome movement; however, it do lead to the forming of considerably (10%) much longer metaphase spindles. From these data we conclude that regular p38 activity is necessary for the timely steady attachment of most kinetochores to spindle microtubules, however, not for the fidelity from the mitotic procedure. We speculate that p38 activity promotes well-timed checkpoint fulfillment by indirectly influencing those electric motor protein (e.g., Klp10, Klp67A) involved with regulating the dynamics of kinetochore microtubule ends. Launch p38, an associate from the mitogen-activated proteins kinase (MAPK) family members, mediates a significant cell routine checkpoint control pathway that guards entrance into mitosis (i.e., the G2/M changeover). This evolutionarily conserved serine/threonine kinase was uncovered in the first 1990s as an integral participant in the cell routine hold off induced by unexpected osmotic adjustments (Brewster (2000) to summarize that the continual activation of p38 arrests fetal mouse thymocytes in mitosis. Nevertheless, more recent inhabitants research on HeLa cells conclude simply the contrary: that inhibiting or depleting p38 qualified prospects to faulty spindles and an arrest in mitosis (Enthusiast (2008) , was custom-made by Dharmacon (Lafayette, CO) to knock down a series of p38 (5-AACTGCGGTTACTTAAACATA-3) that people provided. The various other ON-TARGET plus Wise pool series was supplied by Dharmacon (Catalogue no. L-00351200-00). We also utilized a non-sense control (ON-TARGET plus NonTargeting Pool; Dharmacon D-001810-10). Targeted duplexes had been transfected at 100 nM with oligofectamine (Invitrogen) based on the manufacturer’s guidelines. Occasionally RPE-1 cells had been gathered after a 24C48-h treatment with siRNAs or the non-sense control and lysed with 1 test buffer (62.5 mM Tris, 6 pH.8, 2% SDS, 50 mM DTT, 10% glycerol, 0.01% bromophenol blue) for subsequent immunoblotting. The principal antibody utilized was anti-p38 (no.9212, Cell Signaling, Beverly, MA). Quantification and IMF For IMF microscopy, coverslip civilizations were cleaned with PBS, set with cool 100% methanol (?20C), and permeabilized with 0.5% Triton X-100 in PBS as previously complete (Lee and Tune, 2007 ). The next primary antibodies had been utilized: mouse anti–tubulin (clone GTU-88, Sigma, St. Louis, MO) and rabbit anti-phospho-p38 (no. 9211, Cell Signaling). FITC-conjugated anti-mouse (Sigma) and rabbit Alexa Fluor 568 (Invitrogen) had been utilized as the supplementary antibodies. Picture stacks were obtained and deconvolved on the Delta Vision Program (Applied Accuracy, Issaquah, WA) devoted to an Olympus IX70 microscope (Melville, NY) and built with a CM350 Photometrics camcorder (Huntington Seaside, CA). Phospho-p38 (P-p38) strength was motivated using the technique of Salmon and co-workers (Hoffman (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E10-02-0125) on, may 12, 2010. Sources Adams R. H., Poras A., G Alonso., Jones M., Vintersten K., Panelli S., Valladares A., Perez L., Klein R., Nebreda A. R. Necessary function of p38 MAP kinase in placental however, not embryonic cardiovascular advancement. Mol. Cell. 2000;6:109C116. [PubMed] [Google Scholar]Bacus S. S., Gudkov A. V., Lowe M., Lyass L., Yung Y., Komarov A. P., Keyomarsi K., Yarden Y., Seger R. Taxol-induced apoptosis depends upon MAP kinase pathways (ERK and p38) and it is indie of p53. Oncogene. 2001;20:147C155. [PubMed] [Google Scholar]Bakhoum S. F., Genovese G., Compton D. A. Deviant kinetochore microtubule dynamics underlie chromosomal instability. Curr. Biol. 2009;19:1937C1942. [PMC free of charge content] [PubMed] [Google Scholar]Ben-Levy R., Hooper S., Wilson R., Patterson H. F., Marshall C. J. Nuclear export from the stress-activated proteins kinase p38 mediated by its substrate MAPKAP kinase-2. Curr. Biol. 1998;8:1049C1057. [PubMed] [Google Scholar]Boldt S., Weidle U. H., Kolch W. The function of MAPK pathways in the actions of chemotherapeutic medications. Carcinogenesis. 2002;23:1831C1838. [PubMed] [Google Scholar]Brancho D., Tanaka N., Jaeschke A., Ventura J.-J., Kelkar N., Tanaka Y., Kyuuma M., Takeshita T., Flavell R. A., Davis R. J. System of p38 MAP kinase activation in vivo. Genes Dev. 2003;17:1969C1978. [PMC free of PCI-24781 (Abexinostat) charge content] [PubMed] [Google Scholar]Brewster J. L., de Valoir T., Dwyer N. D., Wintertime E., Gustin M. C. An osmosensing sign transduction pathway in fungus. Research. 1993;259:1760C1763. [PubMed] [Google Scholar]Brito D., Rieder C. L. The capability to survive mitosis in the current presence of microtubule poisons differs considerably between individual nontransformed (RPE-1) and tumor (U2Operating-system, HeLa) cells. Cell Motil. Cytoskelet. 2008;66:437C447. [PMC free of charge content] [PubMed] [Google Scholar]Bulavin D. V., Amundson S. A., Fornace A. J. p38 and Chk1 kinases: different conductors for the G2/M checkpoint symphony. Cur. Opin. Genet. Dev. 2002;12:92C97. [PubMed] [Google Scholar]Bulavin D. V., Higashimoto Y., Popoff I. J., Gaarde W. A., Basrur V., Potapova O., Appella E., Fornace A. J. Initiation of the G2/M checkpoint after ultraviolet rays needs p38 kinase..E., Vale R. cells, we present the prolongation of mitosis in the lack of p38 activity is certainly directly because of a hold off in fulfilling the mitotic checkpoint. Inhibiting p38 didn’t affect the price of chromosome movement; however, it do lead to the forming of considerably (10%) much longer metaphase spindles. From these data we conclude that regular p38 activity is necessary for the timely steady attachment of most kinetochores to spindle microtubules, however, not for the fidelity from the mitotic procedure. We speculate that p38 activity promotes well-timed checkpoint fulfillment by indirectly influencing those electric motor protein (e.g., Klp10, Klp67A) involved with regulating the dynamics of kinetochore microtubule ends. Launch p38, an associate from the mitogen-activated proteins kinase (MAPK) family members, mediates a significant cell routine checkpoint control pathway that guards admittance into mitosis (i.e., the G2/M changeover). This evolutionarily conserved serine/threonine kinase was uncovered in the first 1990s as an integral participant in the cell routine hold off induced by unexpected osmotic adjustments (Brewster (2000) to summarize that the continual activation of p38 arrests fetal mouse thymocytes in mitosis. Nevertheless, more recent inhabitants research on HeLa cells conclude simply the contrary: that inhibiting or depleting p38 qualified prospects to faulty spindles and an arrest in mitosis (Enthusiast (2008) , was custom-made by Dharmacon (Lafayette, CO) to knock down a series of p38 (5-AACTGCGGTTACTTAAACATA-3) that people provided. The various other ON-TARGET plus Wise pool series was supplied by Dharmacon (Catalogue no. L-00351200-00). We also utilized a non-sense control (ON-TARGET plus NonTargeting Pool; Dharmacon D-001810-10). Targeted duplexes had been transfected at 100 nM with oligofectamine (Invitrogen) based on the manufacturer’s guidelines. Occasionally RPE-1 cells had been gathered after a 24C48-h treatment with siRNAs or the non-sense control and lysed with 1 test buffer (62.5 mM Tris, pH 6.8, 2% SDS, 50 mM DTT, 10% glycerol, 0.01% bromophenol blue) for subsequent immunoblotting. The principal antibody utilized was anti-p38 (no.9212, Cell Signaling, Beverly, MA). IMF and Quantification For IMF microscopy, coverslip civilizations were cleaned with PBS, set with cool 100% methanol (?20C), and permeabilized with 0.5% Triton X-100 in PBS as previously complete (Lee and Tune, 2007 ). The next primary antibodies had been utilized: mouse anti–tubulin (clone GTU-88, Sigma, St. Louis, MO) and rabbit anti-phospho-p38 (no. 9211, Cell Signaling). FITC-conjugated anti-mouse (Sigma) and rabbit Alexa Fluor 568 (Invitrogen) had been utilized as the supplementary antibodies. Picture stacks were obtained and deconvolved on the Delta Vision Program (Applied Accuracy, Issaquah, WA) devoted to an Olympus IX70 microscope (Melville, NY) and built with a CM350 Photometrics camcorder (Huntington Seaside, CA). Phospho-p38 (P-p38) strength was motivated using the technique of Salmon and co-workers (Hoffman (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E10-02-0125) on, may 12, 2010. Sources Adams R. H., Poras A., Alonso G., Jones M., Vintersten K., Panelli S., Valladares A., Perez L., Klein R., Nebreda A. R. Necessary function of p38 MAP kinase in placental however, not embryonic cardiovascular advancement. Mol. Cell. 2000;6:109C116. [PubMed] [Google Scholar]Bacus S. S., Gudkov A. V., Lowe M., Lyass L., Yung Y., Komarov A. P., Keyomarsi K., Yarden Y., Seger R. Taxol-induced apoptosis depends upon MAP kinase pathways (ERK and p38) and it is indie of p53. Oncogene. 2001;20:147C155. [PubMed] [Google Scholar]Bakhoum S. F., Genovese G., Compton D. A. Deviant kinetochore microtubule dynamics underlie chromosomal instability. Curr. Biol. 2009;19:1937C1942. [PMC free of charge content] [PubMed] [Google Scholar]Ben-Levy R., Hooper S., Wilson R., Patterson H. F., Marshall C. J. Nuclear export from the stress-activated proteins kinase p38 mediated by its substrate MAPKAP kinase-2. Curr. Biol. 1998;8:1049C1057. [PubMed] [Google Scholar]Boldt S., Weidle U. H., Kolch W. The function of MAPK pathways in the actions of chemotherapeutic medications. Carcinogenesis. 2002;23:1831C1838. [PubMed] [Google Scholar]Brancho D., Tanaka N., Jaeschke A., Ventura J.-J., Kelkar N., Tanaka Y., Kyuuma M., Takeshita T., Flavell R. A., Davis R. J. System of p38 MAP kinase activation in vivo. Genes Dev. 2003;17:1969C1978. [PMC free of charge content] [PubMed] [Google Scholar]Brewster J. L., de Valoir T., Dwyer N. D., Winter E., Gustin M. C. An osmosensing signal transduction pathway in yeast. Science. 1993;259:1760C1763. [PubMed] [Google Scholar]Brito D., Rieder C. L. The ability to survive mitosis in the presence of microtubule.V., Lowe M., Lyass L., Yung Y., Komarov A. spindle microtubules, but not for the fidelity of the mitotic process. We speculate that p38 activity promotes timely checkpoint satisfaction by indirectly influencing those motor proteins (e.g., Klp10, Klp67A) involved in regulating the dynamics of kinetochore microtubule ends. INTRODUCTION p38, a member of the mitogen-activated protein kinase (MAPK) family, mediates a major cell cycle checkpoint control pathway that guards entry into mitosis (i.e., the G2/M transition). This evolutionarily conserved serine/threonine kinase was discovered in the early 1990s as a key player in the cell cycle delay induced by sudden osmotic changes (Brewster (2000) to conclude that the persistent activation of p38 arrests fetal mouse thymocytes in mitosis. However, more recent population studies on HeLa cells conclude just the opposite: that inhibiting or depleting p38 leads to defective spindles and an arrest in mitosis (Fan (2008) , was custom-made by Dharmacon (Lafayette, CO) to knock down a sequence of p38 (5-AACTGCGGTTACTTAAACATA-3) that we provided. The other ON-TARGET plus SMART pool sequence was provided by Dharmacon (Catalogue no. L-00351200-00). We also used a nonsense control (ON-TARGET plus NonTargeting Pool; Dharmacon D-001810-10). Targeted duplexes were transfected at 100 nM with oligofectamine (Invitrogen) according to the manufacturer’s instructions. In some instances RPE-1 cells were harvested after a 24C48-h treatment with siRNAs or the nonsense control and lysed with 1 sample buffer (62.5 mM Tris, pH 6.8, 2% SDS, 50 mM DTT, 10% glycerol, 0.01% bromophenol blue) for subsequent immunoblotting. The primary antibody used was anti-p38 (no.9212, Cell Signaling, Beverly, MA). IMF and Quantification For IMF microscopy, coverslip cultures were washed with PBS, fixed with cold 100% methanol (?20C), and permeabilized with 0.5% Triton X-100 in PBS as previously detailed (Lee and Song, 2007 ). The following primary antibodies were used: mouse anti–tubulin (clone GTU-88, Sigma, St. Louis, MO) and rabbit anti-phospho-p38 (no. 9211, Cell Signaling). FITC-conjugated anti-mouse (Sigma) and rabbit Alexa Fluor 568 (Invitrogen) were used as the secondary antibodies. Image stacks were acquired and deconvolved on a Delta Vision System (Applied Precision, Issaquah, WA) centered on an Olympus IX70 microscope (Melville, NY) and equipped with a CM350 Photometrics camera (Huntington Beach, CA). Phospho-p38 (P-p38) intensity was determined using the method of Salmon and colleagues (Hoffman (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E10-02-0125) on May 12, 2010. REFERENCES Adams R. H., Poras A., Alonso G., Jones M., Vintersten K., Panelli S., Valladares A., Perez L., Klein R., Nebreda A. R. Essential role of p38 MAP kinase in placental but not embryonic cardiovascular development. Mol. Cell. 2000;6:109C116. [PubMed] [Google Scholar]Bacus S. S., Gudkov A. V., Lowe M., Lyass L., Yung Y., Komarov A. P., Keyomarsi K., Yarden Y., Seger R. Taxol-induced apoptosis depends on MAP kinase pathways (ERK and p38) and is independent of p53. Oncogene. 2001;20:147C155. [PubMed] [Google Scholar]Bakhoum S. F., Genovese G., Compton D. A. Deviant kinetochore microtubule dynamics underlie chromosomal instability. Curr. Biol. 2009;19:1937C1942. [PMC free article] [PubMed] [Google Scholar]Ben-Levy R., Hooper S., Wilson R., Patterson H. F., Marshall C. J. Nuclear export of the stress-activated protein kinase p38 mediated by its substrate MAPKAP kinase-2. Curr. Biol. 1998;8:1049C1057. [PubMed] [Google Scholar]Boldt S., Weidle U. H., Kolch W. The role of MAPK pathways in the action of chemotherapeutic drugs. Carcinogenesis. 2002;23:1831C1838. [PubMed] [Google Scholar]Brancho D., Tanaka N., Jaeschke A., Ventura J.-J., Kelkar N., Tanaka Y., Kyuuma M., Takeshita T., Flavell R. A., Davis.Cell Sci. did lead to the formation of significantly (10%) longer metaphase spindles. From these data we conclude that normal p38 activity is required for the timely stable attachment of all kinetochores to spindle microtubules, but not for the fidelity of the mitotic process. We speculate that p38 activity promotes timely checkpoint satisfaction by indirectly influencing those motor proteins (e.g., Klp10, Klp67A) involved in regulating the dynamics of kinetochore microtubule ends. INTRODUCTION p38, a member of the mitogen-activated protein kinase (MAPK) family, mediates a major cell cycle checkpoint control pathway that guards entry into mitosis (i.e., the G2/M transition). This evolutionarily conserved serine/threonine kinase was discovered in the early 1990s as a key player in the cell cycle delay induced by sudden osmotic changes (Brewster (2000) to conclude that the persistent activation of p38 arrests fetal mouse thymocytes in mitosis. However, more recent population studies on HeLa cells conclude just the opposite: that inhibiting or depleting p38 leads to defective spindles and an arrest in mitosis (Fan (2008) , was custom-made by Dharmacon (Lafayette, CO) to knock down a sequence of p38 (5-AACTGCGGTTACTTAAACATA-3) that we provided. The other ON-TARGET plus SMART pool sequence was provided by Dharmacon (Catalogue no. L-00351200-00). We also used a nonsense control (ON-TARGET plus NonTargeting Pool; Dharmacon D-001810-10). Targeted duplexes were transfected at 100 nM with oligofectamine (Invitrogen) according to the manufacturer’s instructions. In some instances RPE-1 cells were harvested after a 24C48-h treatment with siRNAs or the nonsense control and lysed with 1 sample buffer (62.5 mM Tris, pH 6.8, 2% SDS, 50 mM DTT, 10% glycerol, 0.01% bromophenol blue) for subsequent immunoblotting. The primary antibody used was anti-p38 PCI-24781 (Abexinostat) (no.9212, Cell Signaling, Beverly, MA). IMF and Quantification For IMF microscopy, coverslip cultures were washed with PBS, fixed with cold 100% methanol (?20C), and permeabilized with 0.5% Triton X-100 in PBS as previously detailed (Lee and Song, 2007 ). The following primary antibodies were used: mouse anti–tubulin (clone GTU-88, Sigma, St. Louis, MO) and rabbit anti-phospho-p38 (no. 9211, Cell Signaling). FITC-conjugated anti-mouse (Sigma) and rabbit Alexa Fluor 568 (Invitrogen) were used as the secondary antibodies. Image stacks were acquired and deconvolved on a Delta Vision System (Applied Precision, Issaquah, WA) centered on an Olympus IX70 microscope (Melville, NY) and equipped with a CM350 Photometrics video camera (Huntington Beach, CA). Phospho-p38 (P-p38) intensity was identified using the method of Salmon and colleagues (Hoffman (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E10-02-0125) on May 12, 2010. Referrals Adams R. H., Poras A., Alonso G., Jones M., Vintersten K., Panelli S., Valladares A., Perez L., Klein R., Nebreda A. R. Essential part of p38 MAP kinase in placental but not embryonic cardiovascular development. Mol. Cell. 2000;6:109C116. [PubMed] [Google Scholar]Bacus S. S., Gudkov A. V., Lowe M., Lyass L., Yung Y., Komarov A. P., Keyomarsi K., Yarden Y., Seger R. Taxol-induced apoptosis depends on MAP kinase pathways (ERK and p38) and is self-employed of p53. Oncogene. 2001;20:147C155. [PubMed] [Google Scholar]Bakhoum S. F., Genovese G., Compton D. A. Deviant kinetochore microtubule dynamics underlie chromosomal instability. Curr. Biol. 2009;19:1937C1942. [PMC free article] [PubMed] [Google Scholar]Ben-Levy R., Hooper S., Wilson R., Patterson H. F., Marshall C. J. Nuclear export of the stress-activated protein kinase p38 mediated by its substrate MAPKAP kinase-2. Curr. Biol. 1998;8:1049C1057. [PubMed] [Google Scholar]Boldt S., Weidle U. H., Kolch W. The part of MAPK pathways in the action of chemotherapeutic medicines. Carcinogenesis. 2002;23:1831C1838. [PubMed] [Google Scholar]Brancho PCI-24781 (Abexinostat) D., Tanaka N., Jaeschke A., Ventura J.-J., Kelkar N., Tanaka Y.,.1993;104:125C137. kinetochores to spindle microtubules, but not for the fidelity of the mitotic process. We speculate that p38 activity promotes timely checkpoint satisfaction by indirectly influencing those engine proteins (e.g., Klp10, Klp67A) involved in regulating the dynamics of kinetochore microtubule ends. Intro p38, a member of the mitogen-activated protein kinase (MAPK) family, mediates a major cell cycle checkpoint control pathway that guards access into mitosis (i.e., the G2/M transition). This evolutionarily conserved serine/threonine kinase was found out in the early 1990s as a key player in the cell cycle delay induced by sudden osmotic changes (Brewster (2000) to conclude that the prolonged activation of p38 arrests fetal mouse thymocytes in mitosis. However, more recent human population studies on HeLa cells conclude just the opposite: that inhibiting or depleting p38 prospects to defective spindles and an arrest in mitosis (Lover (2008) , was custom-made by Dharmacon (Lafayette, CO) to knock down a sequence of p38 (5-AACTGCGGTTACTTAAACATA-3) that we provided. The additional ON-TARGET plus SMART pool sequence was provided by Dharmacon (Catalogue no. L-00351200-00). We also used a nonsense control (ON-TARGET plus NonTargeting Pool; Dharmacon D-001810-10). Targeted duplexes were transfected at 100 nM with oligofectamine (Invitrogen) according to the manufacturer’s instructions. In some instances RPE-1 cells were harvested after a 24C48-h treatment with siRNAs or the nonsense control and lysed with 1 sample buffer (62.5 mM Tris, pH 6.8, 2% SDS, 50 mM DTT, 10% glycerol, 0.01% bromophenol blue) for subsequent immunoblotting. The primary antibody used was anti-p38 (no.9212, Cell Signaling, Beverly, MA). IMF and Quantification For IMF microscopy, coverslip ethnicities were washed with PBS, fixed with chilly 100% methanol (?20C), and permeabilized with 0.5% Triton X-100 in PBS as previously detailed (Lee and Music, 2007 ). The following primary antibodies were used: mouse anti–tubulin (clone GTU-88, Sigma, St. Louis, MO) and rabbit anti-phospho-p38 (no. 9211, Cell Signaling). FITC-conjugated anti-mouse (Sigma) and rabbit Alexa Fluor 568 (Invitrogen) were used as the secondary antibodies. Image stacks were acquired and deconvolved on a Delta Vision System (Applied Precision, Issaquah, WA) centered on an Olympus IX70 microscope (Melville, NY) and equipped with a CM350 Photometrics video camera (Huntington Beach, CA). Phospho-p38 (P-p38) intensity was identified using the method of Salmon and colleagues (Hoffman (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E10-02-0125) on May 12, 2010. Referrals Adams R. H., Poras A., Alonso G., Jones M., Vintersten K., Panelli S., Valladares A., Perez L., Klein R., Nebreda A. R. Essential part of p38 MAP kinase in placental but not embryonic cardiovascular development. Mol. Cell. 2000;6:109C116. [PubMed] [Google Scholar]Bacus S. S., Gudkov A. V., Lowe M., Lyass L., Yung Y., Komarov A. P., Keyomarsi K., Yarden Y., Seger R. Taxol-induced apoptosis depends on MAP kinase pathways (ERK and p38) and is self-employed of p53. Oncogene. 2001;20:147C155. [PubMed] [Google Rabbit Polyclonal to OR8S1 Scholar]Bakhoum S. F., Genovese G., Compton D. A. Deviant kinetochore microtubule dynamics underlie chromosomal instability. Curr. Biol. 2009;19:1937C1942. [PMC free article] [PubMed] [Google Scholar]Ben-Levy R., Hooper S., Wilson R., Patterson H. F., Marshall C. J. Nuclear export of the stress-activated protein kinase p38 mediated by its substrate MAPKAP kinase-2. Curr. Biol. 1998;8:1049C1057. [PubMed] [Google Scholar]Boldt S., Weidle U. H., Kolch W. The part of MAPK pathways in the action of chemotherapeutic medicines. Carcinogenesis. 2002;23:1831C1838. [PubMed] [Google Scholar]Brancho D., Tanaka N., Jaeschke A., Ventura J.-J., Kelkar N., Tanaka Y., Kyuuma M., Takeshita T., Flavell R. A., Davis R. J. Mechanism of p38 MAP kinase activation in vivo. Genes Dev. 2003;17:1969C1978. [PMC free article] [PubMed] [Google Scholar]Brewster J. L., de Valoir T., Dwyer N. D., Winter E., Gustin M. C. An osmosensing transmission transduction pathway in yeast. Science. 1993;259:1760C1763. [PubMed] [Google Scholar]Brito D., Rieder C. L. The ability to survive mitosis in the presence of microtubule poisons differs significantly between human nontransformed (RPE-1) and malignancy (U2OS, HeLa) cells. Cell Motil. Cytoskelet. 2008;66:437C447. [PMC free article] [PubMed] [Google Scholar]Bulavin D. V., Amundson S. A., Fornace A. J. p38 and Chk1 kinases: different conductors for the G2/M checkpoint symphony. Cur. Opin. Genet. Dev. 2002;12:92C97. [PubMed] [Google Scholar]Bulavin D. V., Higashimoto Y., Popoff I. J., Gaarde W. A., Basrur V., Potapova O., Appella E., Fornace A. J. Initiation of a G2/M checkpoint after ultraviolet radiation requires p38 kinase. Nature. 2001;411:102C107. [PubMed] [Google Scholar]Bunyard P., Handley M., Pollara G., Rutault K., Solid wood I., Chaudry M., Alderman C., Foreman J., Katz D. R., Chain B. M. Ribotoxic stress activates p38 and.