Novel Transcription Coactivator Complex Containing Activating Signal Cointegrator 1

Abstract

Human activating signal cointegrator 1 (hASC-1) was originally isolated as a transcriptional coactivator of nuclear receptors. Here we report that ASC-1 exists as a steady-state complex associated with three polypeptides, P200, P100, and P50, in HeLa nuclei; stimulates transactivation by serum response factor (SRF), activating protein 1 (AP-1), and nuclear factor B (NF-B) through direct binding to SRF, c-Jun, p50, and p65; and relieves the previously described transrepression between nuclear receptors and either AP-1 or NF-B. Interestingly, ectopic expression of Caenorhabditis elegans ASC-1 (ceASC-1), an ASC-1 homologue that binds P200 and P100, like hASC-1, while weakly interacting only with p65, in HeLa cells appears to replace endogenous hASC-1 from the hASC-1 complex and exerts potent dominant-negative effects on AP-1, NF-B, and SRF transactivation. In addition, neutralization of endogenous P50 by single-cell microinjection of a P50 antibody inhibits AP-1 transactivation; the inhibition is relieved by coexpression of wild-type P50, but not of P50⌬KH, a mutant form that does not interact with P200. Overall, these results suggest that the endogenous hASC-1 complex appears to play an essential role in AP-1, SRF, and NF-B transactivation and to mediate the transrepression between nuclear receptors and either AP-1 or NF-B in vivo.

Genes that may modulate longevity in C. elegans in both dauer larvae and long-lived daf-2 adults

“…The asc-1 gene (Y53F4B.15), a homolog of human activating signal cointegrator-1 (Jung et al, 2002), showed an average 28-fold increase in tags (p < 0.001). The non-coding transcribed telomeric sequence (tts-1) transcript (F09E10.11, reported in Jones et al, 2001) was also found at higher levels (average 57 fold increase) in both daf-2 adults and dauer larvae (p < 0.001).…”

A Proteomic Analysis Reveals That Snail Regulates the Expression of the Nuclear Orphan Receptor Nuclear Receptor Subfamily 2 Group F Member 6 (Nr2f6) and Interleukin 17 (IL-17) to Inhibit Adipocyte Differentiation *

“…Trip4, also called activating signal cointegrator 1 (Asc1), is a transcription coactivator of nuclear receptors that plays a pivotal role in the transactivation of NFB and AP1 (44). Trip4 also regulates androgen receptor transactivation and testicular function (45,46).…”

A Truncated Variant of ASCC1, a Novel Inhibitor of NF-κB, Is Associated with Disease Severity in Patients with Rheumatoid Arthritis

“…Nowadays, ASCC1 protein is considered to establish a cross talk with Jun and NF-kB that links inflammatory to tumor suppressive/oncogenic pathways (18). However, very little is known about ASCC1 function and its role in the NF-kB pathway.…”

“…TRIP4 contains a transactivation domain with a putative zinc finger motif, which serves as a binding site for TATA-binding protein, TFIIA, SRC1, CBP/p300, and nuclear receptors (19). It also interacts with a wide range of transcription factors including serum response factor, NF-kB, and AP1, and has been shown to be part of a coactivator complex that links these factors to the transcriptional machinery (18). Overexpressed TRIP4 has been normally local- ized in the nucleus but accumulates in the cytoplasm under serumdeprived conditions (19).…”

“…ASCC1 encodes the p50 subunit of a protein complex, which includes ASCC2, ASCC3, and TRIP4 (also known as ASC1), among others (18) involved in transcriptional regulation. TRIP4 contains a transactivation domain with a putative zinc finger motif, which serves as a binding site for TATA-binding protein, TFIIA, SRC1, CBP/p300, and nuclear receptors (19).…”