CDC2, AND MITOGEN-ACTIVATED PROTEIN-KINASES MODULATE DNA-BINDING PROPERTIES OF THE PUTATIVE TRANSCRIPTIONAL REGULATOR CHIRONOMUS HIGH-MOBILITY GROUP PROTEIN-I
R. Schwanbeck et Jr. Wisniewski, CDC2, AND MITOGEN-ACTIVATED PROTEIN-KINASES MODULATE DNA-BINDING PROPERTIES OF THE PUTATIVE TRANSCRIPTIONAL REGULATOR CHIRONOMUS HIGH-MOBILITY GROUP PROTEIN-I, The Journal of biological chemistry, 272(43), 1997, pp. 27476-27483
Cells of the dipteran insect Chironomus contain a high mobility group
protein that is homologous to the mammalian high mobility group protei
ns I/Y (HMGI/Y). These proteins facilitate the assembly of higher orde
r nucleoprotein complexes, In proliferating cells, >30% of Chironomus
HMGI was found to be phosphorylated, The phosphorylation sites were ma
pped to Ser(3), Ser(22), and Ser(72) and were found to be substrates f
or the kinases Cdc2 (and mitogen-activated protein (MAP)), MAP, and Ca
2+/phospholipid-dependent protein kinase, respectively, In mitotically
arrested cells, the extent of phosphorylation at Ser(3) increased, wh
ereas phosphorylation at Ser(22) remained unchanged, In nondividing ce
lls, phosphorylation at Ser(3) and Ser(22) was strongly reduced, The D
NA binding affinity of Chironomus HMGI was not influenced by single ph
osphorylation at Sers or Ser(22). In contrast, phosphorylation at both
of these sites resulted in a 10-fold weakening of the binding activit
y and altered the mode of protein-DNA interaction. Since both human an
d murine HMGI/Y proteins, similarly to the insect HMGI protein, posses
s phosphorylation sites for Cdc2 and MAP kinases that intersperse the
AT-hook DNA-binding motifs, our results may reflect a general mechanis
m that regulates the properties and function of this class of putative
transcriptional regulators.