C-myc internal ribosome entry site (IRES)

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RF00216

C-myc internal ribosome entry site (IRES) is a crucial regulatory sequence found within the 5' untranslated region (5' UTR) of the c-myc oncogene. The c-myc gene plays a significant role in cell cycle regulation, apoptosis, and cellular transformation, making it a key factor in the development of cancer. The IRES of c-myc enables the ribosome to initiate translation directly at the start codon located within the 5' UTR, bypassing the need for the traditional cap-dependent translation mechanism. This alternative initiation of translation is particularly important under conditions where cap-dependent translation is inhibited, such as during cell stress or apoptosis.

Function and Mechanism[edit | edit source]

The C-myc IRES operates by allowing the recruitment of ribosomes directly to the IRES sequence, facilitating the initiation of translation in a cap-independent manner. This mechanism ensures the continuous production of c-Myc protein under conditions that would normally inhibit protein synthesis, thereby contributing to the oncogene's role in tumorigenesis and cancer progression. The precise molecular mechanisms by which the C-myc IRES mediates translation initiation are complex and involve various IRES trans-acting factors (ITAFs) that modulate its activity.

Clinical Significance[edit | edit source]

Given its role in promoting oncogenesis, the C-myc IRES is a potential target for therapeutic intervention. Inhibiting the function of the C-myc IRES could potentially reduce the expression of the c-Myc protein, thereby hindering the growth and proliferation of cancer cells. Research into small molecules and other compounds that can specifically target and inhibit the C-myc IRES is ongoing, with the hope of developing new anticancer therapies.

Research and Development[edit | edit source]

The study of the C-myc IRES has also provided valuable insights into the broader field of IRES-mediated translation, highlighting the diversity of mechanisms by which cells can regulate protein synthesis. Understanding how IRES elements function under normal and pathological conditions may lead to novel approaches for the treatment of various diseases, beyond just cancer.

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Contributors: Prab R. Tumpati, MD