Artículo

Pelisch, F.; Khauv, D.; Risso, G.; Stallings-Mann, M.; Blaustein, M.; Quadrana, L.; Radisky, D.C.; Srebrow, A. "Involvement of hnRNP A1 in the matrix metalloprotease-3-dependent regulation of Rac1 pre-mRNA splicing" (2012) Journal of Cellular Biochemistry. 113(7):2319-2329
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Abstract:

Rac1b is an alternatively spliced isoform of the small GTPase Rac1 that includes the 57-nucleotide exon 3b. Rac1b was originally identified through its over-expression in breast and colorectal cancer cells, and has subsequently been implicated as a key player in a number of different oncogenic signaling pathways, including tumorigenic transformation of mammary epithelial cells exposed to matrix metalloproteinase-3 (MMP-3). Although many of the cellular consequences of Rac1b activity have been recently described, the molecular mechanism by which MMP-3 treatment leads to Rac1b induction has not been defined. Here we use proteomic methods to identify heterogeneous nuclear ribonucleoprotein (hnRNP) A1 as a factor involved in Rac1 splicing regulation. We find that hnRNP A1 binds to Rac1 exon 3b in mouse mammary epithelial cells, repressing its inclusion into mature mRNA. We also find that exposure of cells to MMP-3 leads to release of hnRNP A1 from exon 3b and the consequent generation of Rac1b. Finally, we analyze normal breast tissue and breast cancer biopsies, and identify an inverse correlation between expression of hnRNP A1 and Rac1b, suggesting the existence of this regulatory axis in vivo. These results provide new insights on how extracellular signals regulate alternative splicing, contributing to cellular transformation and development of breast cancer. © 2012 Wiley Periodicals, Inc.

Registro:

Documento: Artículo
Título:Involvement of hnRNP A1 in the matrix metalloprotease-3-dependent regulation of Rac1 pre-mRNA splicing
Autor:Pelisch, F.; Khauv, D.; Risso, G.; Stallings-Mann, M.; Blaustein, M.; Quadrana, L.; Radisky, D.C.; Srebrow, A.
Filiación:Instituto de Fisiología, Biología Molecular y Neurociencias, Departamento de Fisiología, Biologí́a Molecular y Celular, Universidad de Buenos Aires, Pabellón II, Buenos Aires (C1428EHA), Argentina
Mayo Clinic Cancer Center, Jacksonville, FL 32225, United States
Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires C1428EHA, Argentina
Palabras clave:alternative splicing; hnrnp; matrix metalloprotease; Rac1; heterogeneous nuclear ribonucleoprotein; heterogeneous nuclear ribonucleoprotein A1; messenger RNA; Rac1 protein; stromelysin; unclassified drug; animal cell; article; cell transformation; controlled study; exon; human; human tissue; mouse; nonhuman; priority journal; protein binding; protein expression; protein secretion; proteomics; RNA splicing; signal transduction; Alternative Splicing; Animals; Cell Line, Tumor; Epithelial Cells; Female; Heterogeneous-Nuclear Ribonucleoprotein Group A-B; Mammary Glands, Animal; Mammary Neoplasms, Animal; Matrix Metalloproteinase 3; Mice; Neuropeptides; Protein Isoforms; Proteomics; rac GTP-Binding Proteins; RNA Precursors; RNA Splicing; RNA, Messenger
Año:2012
Volumen:113
Número:7
Página de inicio:2319
Página de fin:2329
DOI: http://dx.doi.org/10.1002/jcb.24103
Título revista:Journal of Cellular Biochemistry
Título revista abreviado:J. Cell. Biochem.
ISSN:07302312
CODEN:JCEBD
CAS:stromelysin, 79955-99-0; Heterogeneous-Nuclear Ribonucleoprotein Group A-B; Matrix Metalloproteinase 3, 3.4.24.17; Neuropeptides; Protein Isoforms; RNA Precursors; RNA, Messenger; Rac1 protein, mouse; hnRNP A1; rac GTP-Binding Proteins, 3.6.5.2
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_07302312_v113_n7_p2319_Pelisch

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Citas:

---------- APA ----------
Pelisch, F., Khauv, D., Risso, G., Stallings-Mann, M., Blaustein, M., Quadrana, L., Radisky, D.C.,..., Srebrow, A. (2012) . Involvement of hnRNP A1 in the matrix metalloprotease-3-dependent regulation of Rac1 pre-mRNA splicing. Journal of Cellular Biochemistry, 113(7), 2319-2329.
http://dx.doi.org/10.1002/jcb.24103
---------- CHICAGO ----------
Pelisch, F., Khauv, D., Risso, G., Stallings-Mann, M., Blaustein, M., Quadrana, L., et al. "Involvement of hnRNP A1 in the matrix metalloprotease-3-dependent regulation of Rac1 pre-mRNA splicing" . Journal of Cellular Biochemistry 113, no. 7 (2012) : 2319-2329.
http://dx.doi.org/10.1002/jcb.24103
---------- MLA ----------
Pelisch, F., Khauv, D., Risso, G., Stallings-Mann, M., Blaustein, M., Quadrana, L., et al. "Involvement of hnRNP A1 in the matrix metalloprotease-3-dependent regulation of Rac1 pre-mRNA splicing" . Journal of Cellular Biochemistry, vol. 113, no. 7, 2012, pp. 2319-2329.
http://dx.doi.org/10.1002/jcb.24103
---------- VANCOUVER ----------
Pelisch, F., Khauv, D., Risso, G., Stallings-Mann, M., Blaustein, M., Quadrana, L., et al. Involvement of hnRNP A1 in the matrix metalloprotease-3-dependent regulation of Rac1 pre-mRNA splicing. J. Cell. Biochem. 2012;113(7):2319-2329.
http://dx.doi.org/10.1002/jcb.24103