Thyroid hormones induce sumoylation of the cold shock domain-containing protein PIPPin in developing rat brain and in cultured neurons

We previously identified a cold shock domain (CSD)-containing protein (PIPPin), expressed at high level in brain cells. PIPPin has the potential to undergo different posttranslational modifications and might be a good candidate to regulate the synthesis of specific proteins in response to extracellular stimuli. Here we report the effects of T-3 on PIPPin expression in developing rat brain. We found that a significant difference among euthyroid and hypothyroid newborn rats concerns sumoylation of nuclear PIPPin, which is abolished by hypothyroidism. Moreover, T-3 dependence of PIPPin sumoylation has been confirmed in cortical neurons purified from brain cortices and cultured in a chemically defined medium (Maat medium), with or without T-3. We also report that about one half of unmodified as well as all the sumoylated form of PIPPin could be extracted from nuclei with HCl, together with histones. Moreover, this HCl-soluble fraction remains in the nucleus even after treatment with 0.6 M KCl, thus suggesting strong interaction of PIPPin with nuclear structures and perhaps chromatin.