Activating signal cointegrator 2 belongs to a novel steady-state complex that contains a subset of trithorax group proteins.
Many transcription coactivators interact with nuclear receptors in a ligand- and C-terminal transactivation function (AF2)-dependent manner. These include activating signal cointegrator 2 (ASC-2), a recently isolated transcriptional coactivator molecule, which is amplified in human cancers and stimulates transactivation by nuclear receptors and numerous other transcription factors. In this report, we show that ASC-2 belongs to a steady-state complex of approximately 2 MDa (ASC-2 complex [ASCOM]) in HeLa nuclei. ASCOM contains retinoblastoma-binding protein RBQ-3, alpha/beta-tubulins, and trithorax group proteins ALR-1, ALR-2, HALR, and ASH2. In particular, ALR-1/2 and HALR contain a highly conserved 130- to 140-amino-acid motif termed the SET domain, which was recently implicated in histone H3 lysine-specific methylation activities. Indeed, recombinant ALR-1, HALR, and immunopurified ASCOM exhibit very weak but specific H3-lysine 4 methylation activities in vitro, and transactivation by retinoic acid receptor appears to involve ligand-dependent recruitment of ASCOM and subsequent transient H3-lysine 4 methylation of the promoter region in vivo. Thus, ASCOM may represent a distinct coactivator complex of nuclear receptors. Further characterization of ASCOM will lead to a better understanding of how nuclear receptors and other transcription factors mediate transcriptional activation.
Goo
Young-Hwa
YH
Department of Life Science, Pohang University of Science and Technology, Korea.
Sohn
Young Chang
YC
Kim
Dae-Hwan
DH
Kim
Seung-Whan
SW
Kang
Min-Jung
MJ
Jung
Dong-Ju
DJ
Kwak
Eunyee
E
Barlev
Nickolai A
NA
Berger
Shelley L
SL
Chow
Vincent T
VT
Roeder
Robert G
RG
Azorsa
David O
DO
Meltzer
Paul S
PS
Suh
Pan-Gil
PG
Song
Eun Joo
EJ
Lee
Kong-Joo
KJ
Lee
Young Chul
YC
Lee
Jae Woon
JW
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D027682:Cation Transport Proteins; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008239:Lysine / Q000378:metabolism; D046911:Macromolecular Substances; D008745:Methylation; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D056918:Nuclear Receptor Coactivators; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism
C110206:ALR1 protein, S cerevisiae; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; C452979:KMT2C protein, human; D046911:Macromolecular Substances; C486559:NCOA6 protein, human; D009687:Nuclear Proteins; D056918:Nuclear Receptor Coactivators; C470552:RBBP5 protein, human; D018168:Receptors, Retinoic Acid; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C063460:Trl protein, Drosophila; D014404:Tubulin; C103604:ash2 protein, Drosophila; D008239:Lysine