Nuclear localisation of endogenous SUMO-1-modified PDGF-C in human thyroid tissue and cell lines

We investigated post-translational modification and subcellular localisation of endogenous platelet-derived growth factor-C (PDGF-C) in human thyroid papillary carcinomas (PTC), non-neoplastic thyroid tissues, and a selection of cultured cell lines. PDGF-C expressed nuclear localisation in 95% of all tested cell types in culture and in 10% of the thyrocytes from both PTC and non-neoplastic tissue. The cell lines expressed two forms of full-length PDGF-C, ∼39 and ∼55 kDa, in cell membrane and cytosol, while the ∼55 kDa form dominated in the nucleus where it was partly chromatin-associated. The ∼55 kDa form was post-translationally modified by SUMO-1. The putative PDGF-C SUMOylation site is the surface exposed 314lysine part of a positively charged loop ( 312RPKTGVRGLHK 322) with characteristics of a nuclear localisation signal. The tissue thyrocytes expressed a non-SUMOylated ∼43 kDa and the 55 kDa PDGF-C. The SUMO-1 modified ∼55 kDa PDGF-C expression was low in PTC where the ∼43 kDa PDGF-C dominated. This is in contrast to non-neoplastic tissue and cultured cells where the SUMOylated ∼55 kDa PDGF-C was strongly expressed. Our data provide novel evidence for nuclear localisation of PDGF-C, post-translational modification by SUMOylation and the expression of a novel form of PDGF-C in human papillary thyroid carcinomas.