TORCs/CRTCs: More than mere coincidence

• Published in: Cell cycle (Georgetown, Tex.) Tex.), 2009-04, Vol.8 (7), p.959-964
• Main Authors: Jean-Sébastien Hulot, David J. Vaux
• Format: Article
• Language: English
• Subjects: Binding; Biology; Bioscience; Calcium; Cancer; Cell; Cycle; Landes; Organogenesis; Proteins
• ISSN: 1538-4101; 1551-4005
• DOI: 10.4161/cc.8.7.8114

Accumulating evidence suggests that the nuclear envelope (NE) is essential for controlling gene expression in health and disease and is not just a passive structural component.  The molecular mechanisms of this regulation include direct interaction of NE with chromatin itself or with mobile regulators such as transcription factors. Until recently, transcription factor sequestration had been attributed largely to lamin A. Work in our laboratory using cells lacking the C-terminus of lamin B1 revealed mislocalisation of the transcription factor Oct-1, which is normally bound to the NE.  The result is dysregulation of Oct-1 targets, an important subset of which are involved in cellular responses to oxidative stress. The mutant cells therefore harbor high levels of reactive oxygen species and are more susceptible to oxidative stress than normal cells.  Mutations in genes coding for NE components cause a group of diseases known collectively as laminopathies, including dystrophies and Hutchinson Gilford Progeria Syndrome. NE abnormalities are also often observed in cancer cells as well as during the normal ageing process.  The mechanism that we have recently unveiled provides insights into the pathological processes contributing to these conditions.