Molecules that modulate Apaf-1 activity

27 páginas, 6 figuras, 1 tablaProgrammed cell death, apoptosis, is a highly regulated cellular pathway, responsible for the elimination of cells in the organism that are no longer needed or extensively damaged. Defects in the regulation of apoptosis could be at the molecular basis of different diseases, either when it is insufficient or excessive. The formation of the macromolecular complex, apoptosome, is a key event in this pathway, which has also been defined as the intrinsic apoptosis pathway. The apoptosome is a holoenzyme multiprotein complex formed by cytochrome c-activated apoptotic protease-activating factor (Apaf-1), dATP, and procaspase-9. Recent studies have produced a wealth of information about the regulation and functions of Apaf-1, but additional studies aimed at elucidating its role as a signaling device at the crosstalk between different signaling pathways are needed to take advantage for the development of modulators of apoptosis pathways and possible therapeutic applications.This work was partially supported by the Spanish Ministry of Science and Innovation (MICINN), grants BIO2004-998, BIO2007-60666, SAF2008-00048, CSD2008-00005, CTQ2007-60601 and the Centro de Investigación Príncipe Felipe. EPP thanks MICINN for a PR2006-0252 fellowship for visiting UCSF. LM is supported by a predoctoral fellowship from MICINN FPI-European Social Fund. MJV is a Ramon y Cajal researcher. We apologize to researchers in this field whose work has not cited in this review due to space limitations or only referred through reviews.Peer reviewe