c-Myc

c-Myc

Myc (c-Myc) is a regulator gene that codes for a transcription factor. The protein encoded by this gene is a multifunctional, nuclear phosphoprotein that plays a role in cell cycle progression, apoptosis and cellular transformation.

c-Myc gene is a common proto-oncogene and has a transcriptional regulator. It belongs to the family of Myc genes that include B-myc, L-myc, N-myc, and s-myc; however, only c-myc, L-myc, and N-myc have neoplastic potential. The c-Myc gene is located on chromosome 8 of humans. The highly conserved sequence in this gene consists of two parts, one part at the carboxyl-terminus of c-Myc and the other at the amino-terminus of c-Myc. The sequence of the c-Myc protein mainly includes three domains: the amino-terminus, the middle region, and the carboxyl-terminus. There are two highly conserved sequences at the amino terminus. These two element structures are referred to as Myc cassettes, namely myc cassette 1 and myc cassette 2, which are composed of amino acid residue sequences between 70-88 and 153-163, respectively. The carboxy terminus of c-Myc contains domains such as helix loop helix (HLH) and leucine zipper (LZ), which are closely related to the biological function of c-Myc. Therefore, c-Myc is a transcriptional regulator with a b/HLH/Zip structure that has both transcriptional activation and transcriptional repression.

c-Myc is involved in the cell cycle, differentiation, protein synthesis and apoptosis of normal cells and tumor cells, and has become a target for current ) enters a phase II clinical trial of neuroendocrine carcinoma. CX-3543 is a fluoroquinolone derivative with anti-tumor activity. CX-3543 disrupts the interaction between the nucleolin protein and a G-quadruplex DNA structure in the ribosomal DNA (rDNA) template. A critical interaction for rRNA biogenesis is overexpressed in cancer cells. Disruption of this G-quadruplex DNA/protein interaction in aberrant rRNA biogenesis may result in the inhibition of ribosome synthesis and tumor cell apoptosis. CX-3543 inhibits c-Myc expression in QBC939 cells. At the same time, CX-3543 inhibites the expression of c-Myc related miRNAs (miR-9, miR-19 and miR-20α). Then it up-regulates the expression of E-cadherin and RB1 of miR-9 and miR-19 target genes, and down-regulates the expression of miR-20α target gene Pten.

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Reference:

Dang, C.V., (1999) c-myc target genes involved in cell growth, apoptosis, and metabolism. Molecular and Cellular Biology, 19 (1): 1-11.

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