Regulatory roles of tumor-suppressor proteins and noncoding RNA in cancer and normal cell functions.
We describe a mechanism for reversible regulation of gene transcription, mediated by a family of tumor-suppressor proteins (TSP) containing a DNA-binding domain (DBD) that binds to a gene and represses transcription, and RNA-binding domains (RBDs) that bind RNA, usually a noncoding RNA (ncRNA), forming a TSP/RNA complex that releases the TSP from a gene and reverses repression. This mechanism appears to be involved in the regulation of embryogenesis, oncogenesis, and steroidogenesis. Embryonic cells express high levels of RNA that bind to a TSP and prevent repression of proto-oncogenes that drive cell proliferation. The level of the RNA subsequently decreases in most differentiating cells, enabling a TSP to repress proto-oncogenes and stop cell proliferation. Oncogenesis can result when the level of the RNA fails to decrease in a proliferating cell or increases in a differentiated cell. This mechanism also regulates transcription of P450scc, the first gene in the steroidogenic pathway.
Garen
Alan
A
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA. alan.garen@yale.edu
Song
Xu
X
D000305:Adrenal Cortex Hormones / Q000235:genetics; D000818:Animals; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004268:DNA-Binding Proteins; D047108:Embryonic Development / Q000235:genetics; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D011519:Proto-Oncogenes; D022661:RNA, Untranslated; D048348:Reverse Transcription; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D000305:Adrenal Cortex Hormones; D004268:DNA-Binding Proteins; D022661:RNA, Untranslated; D025521:Tumor Suppressor Proteins