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Open Access Green as soon as Postprint is submitted to ZB.
Heterogeneous nuclear ribonucleoprotein H blocks MST2-mediated apoptosis in cancer cells by regulating A-Raf transcription.
Cancer Res. 70, 1679-1688 (2010)
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.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Promotes apoptosis; Signaling pathways; Tumor-suppressor; Cycle exit; HNRNP H; B-RAF; BCL-X; Kinase; Drosophila; Activation
ISSN (print) / ISBN
0008-5472
e-ISSN
1538-7445
Journal
Cancer Research
Quellenangaben
Volume: 70,
Issue: 4,
Pages: 1679-1688
Publisher
American Association for Cancer Research (AACR)
Publishing Place
Philadelphia, Pa.
Reviewing status
Peer reviewed
Institute(s)
CCG Molecular Oncology (AGV-KON)