Potential oxygen-dependent regulation of PIAS3

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  • Protein inhibitor of activated STAT3 (PIAS3), a regulator of the JAK/STAT pathway, binds to and blocks the DNA-binding activity of signal transducer and activator of transcription 3 (STAT3). PIAS3 has the potential to be hydroxylated at a specific proline residue, in an amino acid sequence known to be involved in oxygen-dependent post-translational modification of certain proteins, and which may lead to ubiquitination and degradation by the proteasome under normoxia. Alternatively, hydroxylation may affect PIAS3 function, such as its inhibition of STAT3-DNA binding. PIAS3 protein expression was found to be stable regardless of oxygen concentration. However, PIAS3 function increased under hypoxic conditions. Mutation of a specific proline residue was observed to affect the function of PIAS3 in cell growth and proliferation. Protein-protein interactions with PIAS3 were found to change under hypoxic conditions. These results suggest the function of PIAS3 is altered under low oxygen conditions.

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  • Copyright ¬© 2010 the author(s). Theses may be used for non-commercial research, educational, or related academic purposes only. Such uses include personal study, research, scholarship, and teaching. Theses may only be shared by linking to Carleton University Institutional Repository and no part may be used without proper attribution to the author. No part may be used for commercial purposes directly or indirectly via a for-profit platform; no adaptation or derivative works are permitted without consent from the copyright owner.
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  • 2010

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