title: The Diabetes-Linked Transcription Factor PAX4: From Gene to Functional Consequences.
abstract: Paired box 4 (PAX4) is a key factor in the generation of insulin producing β-cells during embryonic development. In adult islets, PAX4 expression is sequestered to a subset of β-cells that are prone to proliferation and more resistant to stress-induced apoptosis. The importance of this transcription factor for adequate pancreatic islets functionality has been manifested by the association of mutations inPAX4with the development of diabetes, independently of its etiology. Overexpression of this factor in adult islets stimulates β-cell proliferation and increases their resistance to apoptosis. Additionally, in an experimental model of autoimmune diabetes, a novel immunomodulatory function for this factor has been suggested. Altogether these data pinpoint at PAX4 as an important target for novel regenerative therapies for diabetes treatment, aiming at the preservation of the remaining β-cells in parallel to the stimulation of their proliferation to replenish the β-cell mass lost during the progression of the disease. However, the adequate development of such therapies requires the knowledge of the molecular mechanisms controlling the expression of PAX4 as well as the downstream effectors that could account for PAX4 action.
authors.affiliation: Pancreatic Islet Development and Regeneration Unit, Department of Cell Regeneration and Advanced Therapies, CABIMER (Junta de Andalucía-CSIC-Universidad de Sevilla-Universidad Pablo de Olavide), Calle Américo Vespucio, 24, 41092 Sevilla, Spain. petra.lorenzo@cabimer.es.
authors.forename: Petra I
authors.initials: PI
authors.lastname: Lorenzo
authors.affiliation: Cell differentiation Lab, Department of Cell Signaling and Dynamics, CABIMER (Junta de Andalucía-CSIC-Universidad de Sevilla-Universidad Pablo de Olavide), Calle Américo Vespucio, 24, 41092 Sevilla, Spain. francisco.juarez@cabimer.es.
authors.forename: Francisco
authors.initials: F
authors.lastname: Juárez-Vicente
authors.affiliation: Pancreatic Islet Development and Regeneration Unit, Department of Cell Regeneration and Advanced Therapies, CABIMER (Junta de Andalucía-CSIC-Universidad de Sevilla-Universidad Pablo de Olavide), Calle Américo Vespucio, 24, 41092 Sevilla, Spain. nadia.cobo@cabimer.es.
authors.forename: Nadia
authors.initials: N
authors.lastname: Cobo-Vuilleumier
authors.affiliation: Cell differentiation Lab, Department of Cell Signaling and Dynamics, CABIMER (Junta de Andalucía-CSIC-Universidad de Sevilla-Universidad Pablo de Olavide), Calle Américo Vespucio, 24, 41092 Sevilla, Spain. mario.garcia@cabimer.es.
authors.forename: Mario
authors.initials: M
authors.lastname: García-Domínguez
authors.affiliation: Pancreatic Islet Development and Regeneration Unit, Department of Cell Regeneration and Advanced Therapies, CABIMER (Junta de Andalucía-CSIC-Universidad de Sevilla-Universidad Pablo de Olavide), Calle Américo Vespucio, 24, 41092 Sevilla, Spain. benoit.gauthier@cabimer.es.
authors.forename: Benoit R
authors.initials: BR
authors.lastname: Gauthier
keywords: PAX4; SUMOylation; diabetes mellitus; regenerative therapy; transcription regulation; β-cell adaptation