GTF3C1 and Associated Diseases
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Backgrounds of GTF3C1
The general transcription factor III (GTF3) family, including GTF3A, GTF3B, GTF3C1, and GTFC2, is known to be involved in the expansion of different types of cancer. GTF3 family members play a crucial role as transcription factors, affecting several important biological pathways. The expression of GTF3 family members plays an important role in the development of malignant tumors. Both yeast and human TFIIIC consist of six peptides that form two globular domains τA and τB. In yeast, all tRNA genes are occupied by TFIIIC; however, in mammalian cells, not all tRNA genes are transcriptionally active. Human TFIIIC can be subdivided into two components: TFIIIC1 and TFIIIC2, which are both required for the transcription of type 1 and type 2 genes. TFIIIC1 is not an assembly factor for TFIIIBβ but is required for the recruitment and initiation of RNA polymerase III. The promoters of RNA polymerase III are recognized by the multisubunit complex TFIIIC, which consists of 200-kDa TFIIIC1 and 600-kDa TFIIIC2.
Fig.1 Transcription of tRNA genes by RNAPIII. (Chymkowitch, 2018)
Functions of GTF3C1
The interaction between GTF3C1 and other genes has been extensively studied. For example, it is involved in pathological networks associated with neurodegeneration and Alzheimer's disease. The GTF3C1 locus is significantly associated with entorhinal cortex thickness, a neuroimaging biomarker associated with Alzheimer's disease. Previous studies have shown that GTF3C1 is involved in the regulation of neuronal nuclear structural rearrangements after neuronal excitation. It is important to note that nuclear architecture plays an important role in neural development and function. GTF3C1 is involved in RNA polymerase III-mediated transcription, microtubule-associated protein 4 (MAP4), which promotes microtubule stability and affects cell growth, and proprotein convertase subtilisin/Kexin type 2 (PC2), which is responsible for the processing of neuropeptide precursors.
GTF3C1 and Associated Diseases
Exploring the potential of GTF3s may be a novel cancer treatment approach to treat colorectal cancer. The expression levels of GTF3B, GTF3C1, and GTF3C2 in colorectal cancer tissues were lower than those in normal tissues. Altered expression of some TFIIIC subunits in mammalian cells has been correlated with infection and disease. GTF3C1 is an immune-related marker for triple-negative breast cancer (TNBC). A TR binding site in the first intron of this gene and the expression of GTF3C1 is upregulated in the cerebellum of hypothyroid animals with TH replacement.
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Reference
- Chymkowitch, P.; Enserink, J.M. Regulation of tRNA synthesis by posttranslational modifications of RNA polymerase III subunits. Biochimica et Biophysica Acta (BBA)-Gene Regulatory Mechanisms. 2018, 1861(4): 310-319.
