Fibroblast Growth Factor 2-Mediated Translational Control of IAPs Blocks Mitochondrial Release of Smac/DIABLO and Apoptosis in Small Cell Lung Cancer Cells

The mitochondrial release of cytochrome c and Smac/DIABLO has been implicated in the activation of apoptosis in response to cell stress. Smac promotes cytochrome c-induced activation of caspases by sequestering the inhibitor of apoptosis protein (IAP) family of potent caspase suppressors. Differential release from mitochondria of cytochrome c and Smac can occur, but the underlying mechanism and physiological significance of this are unclear. Here we show that the mechanism by which fibroblast growth factor 2 (FGF-2) protects small cell lung cancer (SCLC) cells from etoposide-induced cell death involves inhibition of Smac release but not of cytochrome c release. This process is MEK dependent and correlates with an increased expression of XIAP and cellular IAP-1, mediated principally through translational regulation. Exogenous expression of XIAP is sufficient to inhibit caspase 9 activation, Smac release, and cell death induced by etoposide. Prevention of the FGF-2-promoted increase in levels of functional IAPs by RNA interference or the cell-permeant Smac amino-terminal peptide blocked FGF-2-induced protection. FGF-2 can thus protect SCLC cells from chemotherapeutic drugs by modulating IAP levels via posttranscriptional regulation, providing a mechanism for postmitochondrial survival signaling by the MEK/mitogen-activated protein kinase pathway

Changing Multi-level Governance: The Regained Centrality of National Policy-makers in Recasting Pensions in Central Eastern Europe

The chapter focuses on two decades of pension reforms in Central Eastern Europe (CEE). While many analysts have stressed the progressive shift towards multi-level governance, where the World Bank (WB) and the European Union (EU) have increased their influence on national policymakers, evidence from CEE proves national governments have recently re-gained a more central role. While in the 1990s and early 2000s, national policymakers have followed the ‘pension privatisation’ paradigm proposed by International Organisations (IOs); in the wake of the recent economic and financial crisis, some countries have reduced the role of private pension funds while others have continued to privatize their system. Through an actor-centred approach, the present contribution sheds light on the reasons why national governments have re-gained a central role in reforming pensions. In a context marked by weak lock-in mechanisms, actors’ strategies have been crucial to shape governance dynamics. Both national and supra-national actors have altered their governance priorities, and consequently their role in policymaking, on the base of their own political and policy goals. In particular, the changing pensions governance is interpreted to be the consequence of a number of factors: the partial retreat of IOs from the field; the changing policy goals of the EU in the wake of the economic crisis; and the new opportunities for national policymakers to pursue credit-claiming strategies