Tip60 acetyltransferase activity is controlled by phosphorylation.
Here we show that the phosphorylation of histone acetyltransferase Tip60, a target of human immunodeficiency virus, type 1-encoded transactivator Tat, plays a crucial role in the control of its catalytic activity. Baculovirus-based expression and purification of Tip60 combined with mass spectrometry allowed the identification of serines 86 and 90 as two major sites of phosphorylation in vivo. The phosphorylation of Tip60 was found to modulate its histone acetyltransferase activity. One of the identified phosphorylated serines, Ser-90, was within a consensus cyclin B/Cdc2 site. Ser-90 was specifically phosphorylated in vitro by the cyclin B/Cdc2 complex. Accordingly, the phosphorylation of Tip60 was enhanced after drug-induced arrest of cells in G(2)/M. This G(2)/M-dependent phosphorylation of Tip60 was abolished by treating cells with a specific inhibitor of the cyclin-dependent kinase, roscovitin. All together, these results strongly suggest a G(2)/M-dependent control of Tip60 activity.
Lemercier
Claudie
C
Laboratoire de Biologie Moléculaire et Cellulaire de la Différenciation, INSERM U309, Institut Albert Bonniot, Faculté de Médecine, Domaine de la Merci, 38706 La Tronche Cedex, France.
Legube
Gaëlle
G
Caron
Cécile
C
Louwagie
Mathilde
M
Garin
Jérôme
J
Trouche
Didier
D
Khochbin
Saadi
S
D000123:Acetyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D004789:Enzyme Activation / Q000235:genetics; D016195:G2 Phase / Q000502:physiology*; D006367:HeLa Cells; D051548:Histone Acetyltransferases; D006657:Histones / Q000378:metabolism; D006801:Humans; D000074443:Lysine Acetyltransferase 5; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D012694:Serine
D006657:Histones; D012694:Serine; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5