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The Diabetes-Linked Transcription Factor PAX4: From Gene to Functional Consequences

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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
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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
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Authors to whom correspondence should be addressed.
Academic Editor: Bernhard O. Boehm
Genes 2017, 8(3), 101; https://doi.org/10.3390/genes8030101
Received: 30 January 2017 / Revised: 24 February 2017 / Accepted: 3 March 2017 / Published: 9 March 2017
(This article belongs to the Special Issue Genetics and Functional Genomics of Diabetes Mellitus)
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 in PAX4 with 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. View Full-Text
Keywords: PAX4; transcription regulation; SUMOylation; diabetes mellitus; β-cell adaptation; regenerative therapy PAX4; transcription regulation; SUMOylation; diabetes mellitus; β-cell adaptation; regenerative therapy
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Lorenzo, P.I.; Juárez-Vicente, F.; Cobo-Vuilleumier, N.; García-Domínguez, M.; Gauthier, B.R. The Diabetes-Linked Transcription Factor PAX4: From Gene to Functional Consequences. Genes 2017, 8, 101.

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