Modulation of T-cell development in Thessaloniki , Greece Whose Loss Leaves the Immune System Imperilled

The life and health of a cell are dictated by precisely modulated pathways of protein synthesis and degradation. Among these modulatory mechanisms are the extrinsic factors that operate in the cellular environment and the intrinsic pathways that direct the cell from within. Post-translational modification (PTM) of proteins represents one of the many cellautonomous processes of protein regulation that are crucial to the pathophysiology of a cell. The activity of one of the first tumour suppressors to be identified, the Retinoblastoma protein, was, in fact, shown to be modulated by phosphorylation. Likewise, deregulated modification of sugar residues in cell surface glycoproteins disrupts adhesion to basal lamina and results in tumour invasion. Many reports have since investigated the role of a whole plethora of protein modifications right from phosphorylation and acetylation to ubiquitination and sumoylation in health and disease. For over two decades, the research interests of George Mosialos and his colleagues have revolved around the molecular mechanisms of carcinogenesis with a more recent focus on the role of the deubiquitinase cylindromatosis tumour suppressor (Cyld) in T-cell development and leukemogenesis. In their latest paper (J Immunol.,185(4):2032-43), the Mosialos group has uncovered fundamental mechanistic aspects of regulation of T-cell development by CYLD using conditional gene targetting in mice. Their work opens portals to understanding the etiology of T-cell malignancies.