Serine 62-Phosphorylated MYC Associates with Nuclear Lamins and Its Regulation by CIP2A Is Essential for Regenerative Proliferation

An understanding of the mechanisms determining MYC's transcriptional and proliferation-promoting activities in vivo could facilitate approaches for MYC targeting. However, post-translational mechanisms that control MYC function in vivo are poorly understood. Here, we demonstrate that MYC phosphorylation at serine 62 enhances MYC accumulation on Lamin A/C-associated nuclear structures and that the protein phosphatase 2A (PP2A) inhibitor protein CIP2A is required for this process. CIP2A is also critical for serum-induced MYC phosphorylation and for MYC-elicited proliferation induction in vitro. Complementary transgenic approaches and an intestinal regeneration model further demonstrated the in vivo importance of CIP2A and serine 62 phosphorylation for MYC activity upon DNA damage. However, targeting of CIP2A did not influence the normal function of intestinal crypt cells. These data underline the importance of nuclear organization in the regulation of MYC phosphorylation, leading to an in vivo demonstration of a strategy for inhibiting MYC activity without detrimental physiological effects.Peer reviewe

Mental health and work stress: A comparison of response patterns in executive and clerical workers in Hong Kong

Metal health and work stress among 344 clerical (and secretarial) workers and 185 executives (96 managers and 89 executives) in Hong Kong was studied. No overall difference was found between clerical workers and executives in mental health and coping ability when sex was controlled for. Clerical workers, however, reproted fewer interests, more problems in accepting others' values, and more dissatisfaction with work context. Female managers/executives were shown to be a high risk group, reporting more problems in mental health, coping, and work context than their male counterparts. Mental health was strongly associated with each of the work stress factors studied. A significant interaction between sex and nature of job was noted in predictors of mental health. The interaction of coping, context, and mental health is discussed.link_to_subscribed_fulltex