Artículo

Zubeldia-Brenner, L.; Gutierrez-Uzquiza, A.; Barrio-Real, L.; Wang, H.; Kazanietz, M.G.; Leskow, F.C. "β3-Chimaerin, a novel member of the chimaerin Rac-GAP family" (2014) Molecular Biology Reports. 41(4):2067-2076
Estamos trabajando para incorporar este artículo al repositorio
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

Chimaerins are a family of diacylglycerol- and phorbol ester-regulated GTPase activating proteins (GAPs) for the small G-protein Rac. Extensive evidence indicates that these proteins play important roles in development, axon guidance, metabolism, cell motility, and T cell activation. Four isoforms have been reported to-date, which are products of CHN1 (α1- and α2-chimaerins) and CHN2 (β1- and β2-chimaerins) genes. Although these gene products are assumed to be generated by alternative splicing, bioinformatics analysis of the CHN2 gene revealed that β1- and β2-chimaerins are the products of alternative transcription start sites (TSSs) in different promoter regions. Furthermore, we found an additional TSS in CHN2 gene that leads to a novel product, which we named β3-chimaerin. Expression profile analysis revealed predominantly low levels for the β3-chimaerin transcript, with higher expression levels in epididymis, plasma blood leucocytes, spleen, thymus, as well as various areas of the brain. In addition to the prototypical SH2, C1, and Rac-GAP domains, β3-chimaerin has a unique N-terminal domain. Studies in cells established that β3-chimaerin has Rac-GAP activity and is responsive to phorbol esters. The enhanced responsiveness of β3-chimaerin for phorbol ester-induced translocation relative to β2-chimaerin suggests differential ligand accessibility to the C1 domain. © 2014 Springer Science+Business Media Dordrecht.

Registro:

Documento: Artículo
Título:β3-Chimaerin, a novel member of the chimaerin Rac-GAP family
Autor:Zubeldia-Brenner, L.; Gutierrez-Uzquiza, A.; Barrio-Real, L.; Wang, H.; Kazanietz, M.G.; Leskow, F.C.
Filiación:Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, C1428EGA Buenos Aires, Argentina
Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6160, United States
Departamento de Ciencias Básicas, Universidad Nacional de Luján, 6700 Luján Buenos Aires, Argentina
Palabras clave:C1 domain; Chimaerin; CHN2; Phorbol esters; Rac-GAP; alpha1 chimaerin; alpha2 chimaerin; beta1 chimaerin; beta2 chimaerin; beta3 chimaerin; chimerin; guanosine triphosphatase activating protein; isoprotein; phorbol ester; unclassified drug; chimaerin-beta3 protein, human; chimerin; isoprotein; phorbol 13 acetate 12 myristate; protein binding; Rac protein; alternative RNA splicing; amino terminal sequence; article; bioinformatics; CHN1 gene; CHN2 gene; controlled study; enzyme activity; enzyme analysis; epididymis; exon; genetic analysis; human; human cell; human tissue; leukocyte; nucleotide sequence; promoter region; protein analysis; protein domain; protein expression; spleen; thymus; tissue distribution; transcription initiation site; amino acid sequence; animal; antibody specificity; cell line; chemistry; Chlorocebus aethiops; COS 1 cell line; drug effects; enzyme activation; gene expression; gene expression profiling; gene expression regulation; gene order; genetics; metabolism; molecular genetics; Alternative Splicing; Amino Acid Sequence; Animals; Base Sequence; Cell Line; Cercopithecus aethiops; Chimerin Proteins; COS Cells; Enzyme Activation; Gene Expression; Gene Expression Profiling; Gene Expression Regulation; Gene Order; Humans; Molecular Sequence Data; Organ Specificity; Promoter Regions, Genetic; Protein Binding; Protein Interaction Domains and Motifs; Protein Isoforms; rac GTP-Binding Proteins; Tetradecanoylphorbol Acetate
Año:2014
Volumen:41
Número:4
Página de inicio:2067
Página de fin:2076
DOI: http://dx.doi.org/10.1007/s11033-014-3055-3
Título revista:Molecular Biology Reports
Título revista abreviado:Mol. Biol. Rep.
ISSN:03014851
CODEN:MLBRB
CAS:phorbol 13 acetate 12 myristate, 16561-29-8; chimaerin-beta3 protein, human; Chimerin Proteins; Protein Isoforms; rac GTP-Binding Proteins; Tetradecanoylphorbol Acetate
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03014851_v41_n4_p2067_ZubeldiaBrenner

Referencias:

  • Riccomagno, M.M., Hurtado, A., Wang, H., Macopson, J.G.J., Griner, E.M., The RacGAP β2-chimaerin selectively mediates axonal pruning in the hippocampus (2012) Cell, 149, pp. 1594-1606. , 3395473 22726444 10.1016/j.cell.2012.05.018
  • Leskow, F.C., Holloway, B.A., Wang, H., Mullins, M.C., Kazanietz, M.G., The zebrafish homologue of mammalian chimerin Rac-GAPs is implicated in epiboly progression during development (2006) Proc Natl Acad Sci USA, 103, pp. 5373-5378. , 1459362 16569702 10.1073/pnas.0508585103
  • Siliceo, M., Garcia-Bernal, D., Carrasco, S., Diaz-Flores, E., Leskow, F.C., Teixido, J., Kazanietz, M.G., Merida, I., β2-chimaerin provides a diacylglycerol-dependent mechanism for regulation of adhesion and chemotaxis of T cells (2006) Journal of Cell Science, 119 (1), pp. 141-152. , DOI 10.1242/jcs.02722
  • Huang, J.-H., Yang, H.-W., Liu, S., Li, J., Jiang, S., Chen, Y.-H., The mechanism by which molecules containing the HIV-1 gp41 core-binding motif HXXNPF inhibit HIV-1 envelope glycoprotein-mediated syncytium formation (2007) Biochemical Journal, 403 (3), pp. 565-571. , DOI 10.1042/BJ20061275
  • Leung, T., How, B.-E., Manser, E., Lim, L., Germ cell β-chimaerin, a new GTPase-activating protein for p21rac, is specifically expressed during the acrosomal assembly stage in rat testis (1993) Journal of Biological Chemistry, 268 (6), pp. 3813-3816
  • Leung, T., How, B.E., Manser, E., Lim, L., Cerebellar beta 2-chimaerin, a GTPase-activating protein for p21 ras-related rac is specifically expressed in granule cells and has a unique N-terminal SH2 domain (1994) J Biol Chem, 269, pp. 12888-12892. , 8175705
  • Hall, C., Michael, G.J., Cann, N., Ferrari, G., Teo, M., Jacobs, T., Monfries, C., Lim, L., α2-chimaerin, a Cdc42/Rac1 regulator, is selectively expressed in the rat embryonic nervous system and is involved in neuritogenesis in N1E-115 neuroblastoma cells (2001) Journal of Neuroscience, 21 (14), pp. 5191-5202
  • Yuan, S., Miller, D.W., Barnett, G.H., Hahn, J.F., Williams, B.R., Identification and characterization of human beta 2-chimaerin: Association with malignant transformation in astrocytoma (1995) Cancer Res, 55, pp. 3456-3461. , 7614486
  • Wang, H., Yang, C., Leskow, F.C., Sun, J., Canagarajah, B., Phospholipase Cc/diacylglycerol-dependent activation of beta2-chimaerin restricts EGF-induced Rac signaling (2006) EMBO J, 25, pp. 2062-2074. , 1462969 16628218 10.1038/sj.emboj.7601098
  • Colón-González, F., Leskow, F.C., Kazanietz, M.G., Identification of an autoinhibitory mechanism that restricts C1 domain-mediated activation of the Rac-GAP alpha2-chimaerin (2008) J Biol Chem, 283, pp. 35247-35257. , 2596394 18826946 10.1074/jbc.M806264200
  • Griner, E.M., Kazanietz, M.G., Protein kinase C and other diacylglycerol effectors in cancer (2007) Nature Reviews Cancer, 7 (4), pp. 281-294. , DOI 10.1038/nrc2110, PII NRC2110
  • Canagarajah, B., Leskow, F.C., Ho, J.Y.S., Mischak, H., Saidi, L.F., Kazanietz, M.G., Hurley, J.H., Structural mechanism for lipid activation of the Rac-specific GAP, β2-chimaerin (2004) Cell, 119 (3), pp. 407-418. , DOI 10.1016/j.cell.2004.10.012, PII S009286740400995X
  • Griner, E.M., Caino, M.C., Sosa, M.S., Colón-González, F., Chalmers, M.J., A novel cross-talk in diacylglycerol signaling: The Rac-GAP beta2-chimaerin is negatively regulated by protein kinase Cdelta-mediated phosphorylation (2010) J Biol Chem, 285, pp. 16931-16941. , 2878072 20335173 10.1074/jbc.M109.099036
  • Siliceo, M., Mérida, I., T cell receptor-dependent tyrosine phosphorylation of beta2-chimaerin modulates its Rac-GAP function in T cells (2009) J Biol Chem, 284, pp. 11354-11363. , 2670141 19201754 10.1074/jbc.M806098200
  • Batut, P.J., Dobin, A., Plessy, C., Carninci, P., Gingeras, T.R., High-fidelity promoter profiling reveals widespread alternative promoter usage and transposon-driven developmental gene expression (2013) Genome Res, 23 (1), pp. 169-180
  • Rojas-Duran, M.F., Gilbert, W.V., Alternative transcription start site selection leads to large differences in translation activity in yeast (2012) RNA, 18, pp. 2299-2305. , 3504680 23105001 10.1261/rna.035865.112
  • Yang, C., Liu, Y., Leskow, F.C., Weaver, V.M., Kazanietz, M.G., Rac-GAP-dependent inhibition of breast cancer cell proliferation by β2-chimerin (2005) Journal of Biological Chemistry, 280 (26), pp. 24363-24370. , DOI 10.1074/jbc.M411629200
  • Caloca, M.J., Garcia-Bermejo, M.L., Blumberg, P.M., Lewin, N.E., Kremmer, E., Mischak, H., Wang, S., Kazanietz, M.G., β2-Chimaerin is a novel target for diacylglycerol: Binding properties and changes in subcellular localization mediated by ligand binding to its C1 domain (1999) Proceedings of the National Academy of Sciences of the United States of America, 96 (21), pp. 11854-11859. , DOI 10.1073/pnas.96.21.11854
  • Caloca, M.J., Fernandez, N., Lewin, N.E., Ching, D., Modali, R., Blumberg, P.M., Kazanietz, M.G., β2-chimaerin is a high affinity receptor for the phorbol ester tumor promoters (1997) Journal of Biological Chemistry, 272 (42), pp. 26488-26496. , DOI 10.1074/jbc.272.42.26488
  • Dong, J.M., Smith, P., Hall, C., Lim, L., Promoter region of the transcriptional unit for human alpha 1-chimaerin, a neuron-specific GTPase-activating protein for p21rac (1995) Eur J Biochem, 227, pp. 636-646. , 7867622 10.1111/j.1432-1033.1995.tb20183.x
  • Carninci, P., Sandelin, A., Lenhard, B., Katayama, S., Shimokawa, K., Ponjavic, J., Semple, C.A.M., Hayashizaki, Y., Genome-wide analysis of mammalian promoter architecture and evolution (2006) Nature Genetics, 38 (6), pp. 626-635. , DOI 10.1038/ng1789, PII N1789
  • Ayoubi, T.A.Y., Van De Ven, W.J.M., Regulation of gene expression by alternative promoters (1996) FASEB Journal, 10 (4), pp. 453-460
  • Ayoubi, T.A.Y., Creemers, J.W.M., Roebroek, A.J.M., Van De Ven, W.J.M., Expression of the dibasic proprotein processing enzyme furin is directed by multiple promoters (1994) Journal of Biological Chemistry, 269 (12), pp. 9298-9303
  • Schibler, U., Sierra, F., Alternative promoters in developmental gene expression (1987) Annu Rev Genet, 21, pp. 237-257. , 2450521 10.1146/annurev.ge.21.120187.001321
  • Davuluri, R.V., Grosse, I., Zhang, M.Q., Computational identification of promoters and first exons in the human genome (2001) Nature Genetics, 29 (4), pp. 412-417. , DOI 10.1038/ng780
  • A user's guide to the encyclopedia of DNA elements (ENCODE) (2011) PLoS Biol, 9, p. 1001046. , ENCODE Project Consortium 10.1371/journal.pbio.1001046
  • Rada-Iglesias, A., Ameur, A., Kapranov, P., Enroth, S., Komorowski, J., Gingeras, T.R., Wadelius, C., Whole-genome maps of USF1 and USF2 binding and histone H3 acetylation reveal new aspects of promoter structure and candidate genes for common human disorders (2008) Genome Research, 18 (3), pp. 380-392. , http://www.genome.org/cgi/reprint/18/3/380, DOI 10.1101/gr.6880908
  • Rada-Iglesias, A., Wallerman, O., Koch, C., Ameur, A., Enroth, S., Clelland, G., Wester, K., Wadelius, C., Binding sites for metabolic disease related transcription factors inferred at base pair resolution by chromatin immunoprecipitation and genomic microarrays (2005) Human Molecular Genetics, 14 (22), pp. 3435-3447. , DOI 10.1093/hmg/ddi378
  • Ernst, J., Kellis, M., Discovery and characterization of chromatin states for systematic annotation of the human genome (2010) Nat Biotechnol, 28, pp. 817-825. , 2919626 20657582 10.1038/nbt.1662
  • Gardiner-Garden, M., Frommer, M., CpG islands in vertebrate genomes (1987) Journal of Molecular Biology, 196 (2), pp. 261-282
  • Beg, A.A., Sommer, J.E., Martin, J.H., Scheiffele, P., α2-Chimaerin Is an Essential EphA4 Effector in the Assembly of Neuronal Locomotor Circuits (2007) Neuron, 55 (5), pp. 768-778. , DOI 10.1016/j.neuron.2007.07.036, PII S0896627307005818
  • Caloca, M.J., Wang, H., Delemos, A., Wang, S., Kazanietz, M.G., Phorbol esters and related analogs regulate the subcellular localization of beta 2-chimaerin, a non-protein kinase C phorbol ester receptor (2001) J Biol Chem, 276, pp. 18303-18312. , 11278894 10.1074/jbc.M011368200
  • Penas-Steinhardt, A., Barcos, L.S., Belforte, F.S., De Sereday, M., Vilariño, J., Functional characterization of TLR4 +3725 G/C polymorphism and association with protection against overweight (2012) PLoS One, 7, p. 50992. , 3519812 23239997 10.1371/journal.pone.0050992
  • Wang, H., Kazanietz, M.G., P23/Tmp21 differentially targets the Rac-GAP beta2-chimaerin and protein kinase C via their C1 domains (2010) Mol Biol Cell, 21, pp. 1398-1408. , 2854097 20164256 10.1091/mbc.E09-08-0735
  • Menna, P.L., Skilton, G., Leskow, F.C., Alonso, D.F., Gomez, D.E., Kazanietz, M.G., Inhibition of aggressiveness of metastatic mouse mammary carcinoma cells by the β2-chimaerin GAP domain (2003) Cancer Research, 63 (9), pp. 2284-2291
  • Miyake, N., Chilton, J., Psatha, M., Cheng, L., Andrews, C., Human CHN1 mutations hyperactivate alpha2-chimaerin and cause Duane's retraction syndrome (2008) Science, 321, pp. 839-843. , 2593867 18653847 10.1126/science.1156121
  • Caloca, M.J., Wang, H., Kazanietz, M.G., Characterization of the Rac-GAP (Rac-GTPase-activating protein) activity of β2-chimaerin, a 'non-protein kinase C' phorbol ester receptor (2003) Biochemical Journal, 375 (2), pp. 313-321. , DOI 10.1042/BJ20030727
  • Gutierrez-Uzquiza, A., Colon-Gonzalez, F., Leonard, T.A., Canagarajah, B.J., Wang, H., Mayer, B.J., Hurley, J.H., Kazanietz, M.G., Coordinated activation of the Rac-GAP β2-chimaerin by an atypical proline-rich domain and diacylglycerol (2013) Nat Commun, 4, p. 1849. , 3700536 23673634 10.1038/ncomms2834

Citas:

---------- APA ----------
Zubeldia-Brenner, L., Gutierrez-Uzquiza, A., Barrio-Real, L., Wang, H., Kazanietz, M.G. & Leskow, F.C. (2014) . β3-Chimaerin, a novel member of the chimaerin Rac-GAP family. Molecular Biology Reports, 41(4), 2067-2076.
http://dx.doi.org/10.1007/s11033-014-3055-3
---------- CHICAGO ----------
Zubeldia-Brenner, L., Gutierrez-Uzquiza, A., Barrio-Real, L., Wang, H., Kazanietz, M.G., Leskow, F.C. "β3-Chimaerin, a novel member of the chimaerin Rac-GAP family" . Molecular Biology Reports 41, no. 4 (2014) : 2067-2076.
http://dx.doi.org/10.1007/s11033-014-3055-3
---------- MLA ----------
Zubeldia-Brenner, L., Gutierrez-Uzquiza, A., Barrio-Real, L., Wang, H., Kazanietz, M.G., Leskow, F.C. "β3-Chimaerin, a novel member of the chimaerin Rac-GAP family" . Molecular Biology Reports, vol. 41, no. 4, 2014, pp. 2067-2076.
http://dx.doi.org/10.1007/s11033-014-3055-3
---------- VANCOUVER ----------
Zubeldia-Brenner, L., Gutierrez-Uzquiza, A., Barrio-Real, L., Wang, H., Kazanietz, M.G., Leskow, F.C. β3-Chimaerin, a novel member of the chimaerin Rac-GAP family. Mol. Biol. Rep. 2014;41(4):2067-2076.
http://dx.doi.org/10.1007/s11033-014-3055-3