Oncoproteins

Oncoproteins are proteins that contribute to cancer development when they are abnormally expressed or mutated. They can be encoded by cellular oncogenes, which arise from proto-oncogenes that have been activated by mutation, amplification, or chromosomal rearrangement, or by viral genes that integrate into host genomes. By altering signaling and transcriptional programs, oncoproteins promote unchecked cell proliferation, survival, and other cancer-related traits.

Cellular oncogenes include RAS (KRAS, HRAS, NRAS), which activate the MAPK and PI3K pathways; MYC, a transcription factor that drives growth; ERBB2/HER2, a receptor tyrosine kinase; and BCR-ABL, a fusion protein with constitutive kinase activity. These proteins can push cells through the cell cycle, prevent apoptosis, reprogram metabolism, or enhance angiogenesis.

Viral oncoproteins: HPV E6 and E7 inactivate tumor suppressors p53 and Rb, respectively, removing checkpoints on growth and genome integrity. SV40 large T antigen and adenovirus E1A/E1B disrupt similar safeguards, cooperating with other mutations to foster transformation.

Mechanisms and pathways: Oncoproteins commonly act through receptor tyrosine kinases, Ras-MAPK, PI3K-AKT, NF-κB signaling, and transcriptional networks such as Myc targets. They can alter cyclin-dependent kinase activity, reduce p53-mediated apoptosis, and promote genomic instability.

Clinical relevance: Oncoproteins are central targets in cancer therapy and diagnosis. Inhibitors of BCR-ABL, EGFR, and HER2 exemplify this approach; other strategies aim to disrupt Myc-driven transcription or downstream survival pathways. Oncoprotein status can aid prognosis and guide treatment decisions.