A link between apoptosis and degree of phosphorylation of high mobility group A1a protein in leukemic cells

Nuclear phosphoprotein HMGA1a, high mobility group A1a, (previously HMGI) h as been investigated during apoptosis. A change in the degree of phosphoryl ation of HMGA1a has been observed during apoptosis induced in four leukemic cell lines (HL60, K562, NB4, and U937) by drugs (etoposide, camptothecin) or herpes simplex virus type-1. Both hyper-phosphorylation and de-phosphory lation of HMGA1a have been ascertained by liquid chromatography-mass spectr ometry. Hyperphosphorylation (at least five phosphate groups/ HMGA1a molecu le) occurs at the early apoptotic stages and is probably related to HMGA1a displacement from DNA and chromatin release from the nuclear scaffold. De-p hosphorylation (one phosphate or no phosphate groups/HMGA1a molecule) accom panies the later formation of highly condensed chromatin in the apoptotic b odies. We report for the first time a direct link between the degree of pho sphorylation of HMGA1a protein and apoptosis according to a process that in volves the entire amount of HMGA1a present in the cells and, consequently, whole chromatin. At the same time we report that variously phosphorylated f orms of HMGA1a protein are also mono-methylated.