Heterogeneous Nuclear Ribonucleoprotein H Blocks MST2-Mediated Apoptosis in Cancer Cells by Regulating a-raf Transcription
2010 | journal article. A publication with affiliation to the University of Göttingen.
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Heterogeneous Nuclear Ribonucleoprotein H Blocks MST2-Mediated Apoptosis in Cancer Cells by Regulating a-raf Transcription
Rauch, J.; O'Neill, E.; Mack, B.; Matthias, C.; Munz, M.; Kolch, W. & Gires, O. (2010)
Cancer Research, 70(4) pp. 1679-1688. DOI: https://doi.org/10.1158/0008-5472.CAN-09-2740
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- Authors
- Rauch, Jens; O'Neill, Eric; Mack, Brigitte; Matthias, Christoph; Munz, Markus; Kolch, Walter; Gires, Olivier
- Abstract
- A-Raf belongs to the family of oncogenic Raf kinases that are involved in mitogenic signaling by activating the mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinase (MEK)-ERK pathway. Low kinase activity of A-Raf toward MEK suggested that A-Raf might have alternative functions. Here, we show that A-Raf prevents cancer cell apoptosis contingent on the expression of the heterogeneous nuclear ribonucleoprotein H (hnRNP H) splice factor, which is required for the correct transcription and expression of a-raf. Apoptosis was prevented by A-Raf through sequestration and inactivation of the proapoptotic MST2 kinase. Small interfering RNA-mediated knockdown of hnRNP H or A-Raf resulted in MST2-dependent apoptosis. In contrast, enforced expression of either hnRNP H or A-Raf partially counteracted apoptosis induced by etoposide. In vivo expression studies of colon specimens corroborated the overexpression of hnRNP H in malignant tissues and its correlation with A-Raf levels. Our findings define a novel mechanism that is usurped in tumor cells to escape naturally imposed apoptotic signals. Cancer Res; 70(4); 1679-88. (C) 2010 AACR.
- Issue Date
- 2010
- Status
- published
- Publisher
- Amer Assoc Cancer Research
- Journal
- Cancer Research
- ISSN
- 0008-5472