In Silico Analysis of Pax6 Interacting Proteins Indicates Missing Molecular Links in Development of Brain and Associated Disease
The PAX6, a transcription factor, is essential for the morphogenesis of the eyes, brain, pituitary and pancreatic islets. In rodents, the loss of Pax6 function leads to central nervous system defects, anophthalmia, and nasal hypoplasia. The haplo-insufficiency of Pax6 causes microphthalmia, aggression and other behavioral abnormalities. It is also required in brain patterning and neuronal plasticity. In human, heterozygous mutation of Pax6 causes loss of iris [aniridia], mental retardation and glucose intolerance. The 3- deletion in Pax6 leads to autism and aniridia. The phenotypes are variable in peneterance and expressivity. However, mechanism of function and interaction of PAX6 with other proteins during development and associated disease are not clear. It is intended to explore interactors of PAX6 to elucidated biology of PAX6 function in the tissues where it is expressed and also in the central regulatory pathway. This report describes In-silico approaches to explore interacting proteins of PAX6. The models show several possible proteins interacting with PAX6 like MITF, SIX3, SOX2, SOX3, IPO13, TRIM, and OGT. Since the Pax6 is a critical transcriptional regulator and master control gene of eye and brain development it might be interacting with other protein involved in morphogenesis [TGIF, TGF, Ras etc]. It is also presumed that matricelluar proteins [SPARC, thrombospondin-1 and osteonectin etc] are likely to interact during transport and processing of PAX6 and are somewhere its cascade. The proteins involved in cell survival and cell proliferation can also not be ignored.
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