Merlin Represses Ras-Induced Cyclin D1 Transcription through the Cyclic AMP-Responsive Element.
- Author:
Noh Jin KWAK
1
;
Hongtae KIM
;
Byung Hyune CHOI
;
Young Hoon KIM
;
Hyoung Kyun RHA
;
Kweon Haeng LEE
Author Information
1. Neuroscience Genome Research Center, The Catholic University of Korea, 505 Banpo-dong, Socho-gu, Seoul 137-701, Korea.
- Publication Type:Original Article
- Keywords:
Neurofibromatosis type 2 (NF2);
Ha-ras;
Cyclin D1;
cAMP-responsive element
- MeSH:
Cell Proliferation;
Cyclin D1*;
Cyclins*;
Genes, Tumor Suppressor;
Nervous System Neoplasms;
Neuroblastoma;
Neurofibromatosis 2;
Neurofibromin 2*;
Repression, Psychology
- From:The Korean Journal of Physiology and Pharmacology
2003;7(5):289-293
- CountryRepublic of Korea
- Language:English
-
Abstract:
Mutations in the NF2 tumor suppressor gene cause neurofibromatosis type 2, an autosomal dominant inherited syndrome predisposed to the multiple tumors of the nervous system. Merlin, the NF2 gene product was reported to block Ras-mediated cell transformation and represses Ras-induced expression of cyclin D1. However, the potential mechanism underlying the anti-Ras function of merlin on the cyclin D1 is still unclear. In this study, we investigated whether merlin decreases Ha-ras-induced accumulation of cyclin D1 at the transcriptional level, and demonstrated that merlin suppressed Ras-induced cyclin D1 promoter activity mediated by the cyclic AMP-responsive element (CRE) in SK-N-BE (2) C neuroblastoma cells. Furthermore, we found that merlin attenuated active Ras and forskolin-induced CRE-driven promoter activity. These results suggest that the transcriptional repression of the cyclin D1 expression by merlin may contribute to the inhibition of Ras-induced cell proliferation
