Post-Translational Modifications in Cancer Progression: Focus on Phosphorylation and Ubiquitination

Post-translational modifications (PTMs) are crucial regulators of protein function and play a pivotal role in cancer progression. Among the diverse array of PTMs, phosphorylation and ubiquitination are particularly important in the regulation of key cellular processes, such as cell cycle progression, apoptosis, and signal transduction. Phosphorylation, the addition of phosphate groups to proteins, modulates protein activity, stability, and interactions, with dysregulation often leading to oncogenic signaling. Similarly, ubiquitination, the attachment of small ubiquitin molecules to target proteins, marks them for degradation or alters their cellular localization, thereby influencing critical pathways involved in tumor growth, metastasis, and resistance to therapy. This review examines the role of phosphorylation and ubiquitination in cancer progression, focusing on their involvement in regulating key oncogenic pathways, such as the PI3K-Akt-mTOR pathway, the MAPK pathway, and the p53 tumor suppressor pathway. We also explore how these PTMs contribute to the development of cancer hallmarks, including evading growth suppressors, enabling replicative immortality, and resisting cell death. The review further discusses therapeutic strategies aimed at targeting the enzymes involved in these modifications, such as kinase inhibitors and proteasome inhibitors, and highlights the potential for developing combination therapies to overcome resistance. Understanding the precise molecular mechanisms by which phosphorylation and ubiquitination contribute to cancer progression provides opportunities for novel therapeutic interventions in oncology.