Possible role of transcriptional coactivator P/CAF and nuclear acetylation in calcium-induced keratinocyte differentiation.
Several nuclear factors, called coactivators, such as CREB (cAMP response element binding protein)-binding protein (CBP) and p300/CBP associated factor (P/CAF), have intrinsic histone acetyltransferase (HAT) activity. Recent studies have shown that, in addition to histones, transcriptional regulatory molecules are also targets of HATs, and nuclear acetylation is thought to be involved in several biological events. We observed that a high concentration of calcium induced HAT activity in the keratinocyte cell line, HaCaT. The steady-state level of specific acetylated nuclear proteins changed in a dynamic fashion in HaCaT cells induced with 1.2 mm calcium. One (approximately 97-kDa acetylated protein designated as ap97) was transiently induced, one (ap78) was induced and then continuously expressed, and one (ap70) disappeared with time. Although the up-regulation of ap70 and ap78 was not influenced by GF109203X, a specific inhibitor of protein kinase C (PKC), the calcium-induced accumulation of ap97 and the induction of P/CAF HAT activity were similarly attenuated by GF109203X. Notably, mutant P/CAF lacking HAT activity repressed the expression of ap97 and involucrin, a keratinocyte differentiation marker. Our results suggest that P/CAF HAT activity and induction of ap97 are involved in calcium-dependent keratinocyte differentiation.
Kawabata
Hisashi
H
Department of Dermatology and Laboratory of Molecular Medicine, Kagoshima University, Faculty of Medicine, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
Kawahara
Ko-ichi
K
Kanekura
Takuro
T
Araya
Natsumi
N
Daitoku
Hiroaki
H
Hatta
Mitsutoki
M
Miura
Naoki
N
Fukamizu
Akiyoshi
A
Kanzaki
Tamotsu
T
Maruyama
Ikuro
I
Nakajima
Toshihiro
T
D000123:Acetyltransferases / Q000737:chemistry* / Q000378:metabolism*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019084:Fluorescent Antibody Technique, Indirect; D051548:Histone Acetyltransferases; D006657:Histones / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism*; D008301:Maleimides / Q000494:pharmacology; D009154:Mutation; D011233:Precipitin Tests; D011485:Protein Binding; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011498:Protein Precursors / Q000494:pharmacology; D013997:Time Factors; D014157:Transcription Factors; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D002118:Calcium; D018797:Cell Cycle Proteins; D004247:DNA; D004791:Enzyme Inhibitors; D051548:Histone Acetyltransferases; D006657:Histones; D007211:Indoles; D008301:Maleimides; D011493:Protein Kinase C; D011498:Protein Precursors; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C032253:involucrin; C070515:bisindolylmaleimide I