Upregulation of HMG1 Leads to Melanoma Inhibitory Activity Expression in Malignant Melanoma Cells and Contributes to Their Malignancy Phenotype
AUTOR(ES)
Poser, Ina
FONTE
American Society for Microbiology
RESUMO
Malignant transformation of melanocytes to melanoma cells closely parallels activation of melanoma inhibitory activity (MIA) expression. We have previously shown that upregulation of MIA occurs on a transcriptional level and involves the highly conserved region (HCR) promoter element. We further observed that the HCR element interacts with the melanoma-associated transcription factor (MATF) and thereby confers strong promoter activation. In this study we identify the peptide sequence of MATF and show that it is identical with the transcription factor HMG1. HMG1 was upregulated in malignant melanoma cells and further activated by hypophosphorylation. Stable antisense-HMG1 expression in melanoma cells led to the reduction of MIA promoter activity and protein expression, indicating that HMG1 is a potent regulator of MIA expression. Interestingly, chromatin immunoprecipitation and electrophoretic mobility shift experiments indicated that HMG1 and the NF-κB family member p65 both interact and bind to the HCR promoter element. In summary, our study proves HMG1 and p65 to be important factors in MIA regulation and melanoma progression.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=152547Documentos Relacionados
- High affinity binding of proteins HMG1 and HMG2 to semicatenated DNA loops
- Increased manganese superoxide dismutase expression suppresses the malignant phenotype of human melanoma cells.
- Steroid hormones induce HMG1 overexpression and sensitize breast cancer cells to cisplatin and carboplatin
- HMG1 interacts with HOX proteins and enhances their DNA binding and transcriptional activation.
- Nonhistone proteins HMG1 and HMG2 unwind DNA double helix.