Sinnberg, Tobias and Sauer, Birgit and Holm, Per and Spangler, Barbara and Kuphal, Silke and Bosserhoff, Anja and Schittek, Birgit (2012) MAPK and PI3K/AKT mediated YB-1 activation promotes melanoma cell proliferation which is counteracted by an autoregulatory loop. EXPERIMENTAL DERMATOLOGY, 21 (4). pp. 265-270. ISSN 0906-6705,
Full text not available from this repository. (Request a copy)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 NF?B 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BOX-BINDING PROTEIN-1; BREAST-CANCER CELLS; NUCLEAR-LOCALIZATION; MESSENGER-RNA; SIGNALING PATHWAYS; DRUG-RESISTANCE; TRANSLATION; INHIBITION; EXPRESSION; GROWTH; MAPK signalling; melanoma; NF?B signalling; PI3K signalling; YB-1 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 May 2020 11:38 |
| Last Modified: | 15 May 2020 11:38 |
| URI: | https://pred.uni-regensburg.de/id/eprint/18970 |
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