Beclin-1 and its role as a target for anticancer therapy

The nomenclature committee on cell death (nccd,2009) defines different types of cell death on the basis of morphological,enzymological,immunological and functional criteria. four basic types of cell death are distinguished from the biochemical point of view: necrosis,apoptosis,autophagy and cornification. autophagy (macroautophagy) is a highly conserved process by which defective organelles,non-functional proteins and lipids become sequestered within structures called autophagosomes,which fuse with lysosomes,and the engulfed components are then degraded by lysosomal enzymes. the role of autophagy is not only the elimination of components,it also serves as a dynamic recycling system that produces new materials and energy for cellular renovation and homeostasis. beclin-1 is a protein that plays a central role in autophagy; it interacts with multiple cofactors (atg14l,uvrag,bif-1,rubicon,ambra1,hmgb1,ip3r,pink and survivin) to promote the formation of the beclin-1-vps34-vps15 complex which triggers the autophagy protein cascade. beclin-1 dysfunction may lead to immune disorders,liver and neurodegenerative diseases as well as cancer. a positive and negative correlation between the expression pattern and/or activity of beclin-1 and carcinogenesis has been demonstrated. here we describe recent advances in understanding the molecular dynamics and regulation of autophagy and we discuss beclin-1's contribution to anticancer therapy.