MAPK and PI3K/AKT mediated YB-1 activation promotes melanoma cell proliferation which is counteracted by an autoregulatory loop
Sinnberg T, Sauer B, Holm P, Spangler B, Kuphal S, Bosserhoff A, Schittek B (2012)
Publication Type: Journal article
Publication year: 2012
Journal
Book Volume: 21
Pages Range: 265-270
Journal Issue: 4
DOI: 10.1111/j.1600-0625.2012.01448.x
Abstract
Y-box binding protein 1 (YB-1) is an oncogenic transcription and translation factor and is overexpressed in several types of cancer. Our previous data showed that YB-1 is upregulated and translocated to the nucleus during melanoma progression and that YB-1 is an important transcription factor regulating proliferation, survival, migration, invasion and chemosensitivity of melanoma cells. It has been suggested that YB-1 is activated and translocated to the nucleus after S102-phosphorylation in the DNA binding domain. In this study, we show that activation of YB-1 by S102-phosphorylation and nuclear translocation is increased during melanoma progression using a human tissue microarray with 100 melanocytic lesions. Furthermore, we analysed the mechanisms governing the expression and activity of YB-1 in melanoma cells. We show that the PI3K/AKT and p53 signalling, growth factors and chemotherapeutic agents increase YB-1 promoter activity. This, however, resulted in no or only modest increase in YB-1 protein expression. We show that the MAPK and PI3K/AKT signalling pathways, both activated in melanoma cells, as well as p53 overexpression increase YB-1 S102-phosphorylation, whereas NFκB signalling inhibits phosphorylation. Overexpression of YB-1 in melanoma cells inhibits translation efficiency and by this proliferation and survival of melanoma cells indicating that there is an autoregulatory loop restricting YB-1 protein expression. These data suggest that there is a tightly regulated feedback mechanism regulating YB-1 expression and activation, necessary for proper cell cycle progression of melanoma cells. © 2012 John Wiley & Sons A/S.
Involved external institutions
Eberhard Karls Universität Tübingen
Germany (DE)
Technische Universität München (TUM)
Germany (DE)
Universität Regensburg
Germany (DE)
Germany (DE)
Technische Universität München (TUM)
Germany (DE)
Universität Regensburg
Germany (DE)
How to cite
APA:
Sinnberg, T., Sauer, B., Holm, P., Spangler, B., Kuphal, S., Bosserhoff, A., & Schittek, B. (2012). MAPK and PI3K/AKT mediated YB-1 activation promotes melanoma cell proliferation which is counteracted by an autoregulatory loop. Experimental Dermatology, 21(4), 265-270. https://doi.org/10.1111/j.1600-0625.2012.01448.x
MLA:
Sinnberg, Tobias, et al. "MAPK and PI3K/AKT mediated YB-1 activation promotes melanoma cell proliferation which is counteracted by an autoregulatory loop." Experimental Dermatology 21.4 (2012): 265-270.
BibTeX: Download