{
    "title": "Purification and identification of p68 RNA helicase acting as a transcriptional coactivator specific for the activation function 1 of human estrogen receptor alpha.",
    "journal": "Mol. Cell. Biol.",
    "date": "1999",
    "authors": "Maruyama K., Kobayashi Y., Hashimoto S., Kato S., Goto M., Endoh H., Yanagisawa J., Masuhiro Y., Metzger D., Tai H.",
    "reference": {
        "type": "PubMed",
        "id": "10409727",
        "url": "https://pubmed.ncbi.nlm.nih.gov/10409727"
    },
    "referenced_proteins": [
        "P03372-1",
        "P17844-1"
    ],
    "referenced_glycans": [],
    "species": [
        {
            "name": "Homo sapiens",
            "taxid": 9606,
            "evidence": [
                {
                    "database": "UniProtKB",
                    "id": "P03372",
                    "url": "https://www.uniprot.org/uniprot/P03372"
                }
            ],
            "common_name": "Human"
        }
    ],
    "mutagenesis": [
        {
            "start_pos": 118,
            "end_pos": 118,
            "sequence_org": "S",
            "sequence_mut": "A",
            "comment": "Decreases phosphorylation and transactivation activity. Abolishes AF-1 transactivation. Insensitive to PPP5C inhibition of transactivation activity.",
            "evidence": [
                {
                    "database": "UniProtKB",
                    "id": "P03372",
                    "url": "https://www.uniprot.org/uniprot/P03372"
                },
                {
                    "database": "PubMed",
                    "id": "14764652",
                    "url": "https://pubmed.ncbi.nlm.nih.gov/14764652"
                },
                {
                    "database": "PubMed",
                    "id": "10409727",
                    "url": "https://pubmed.ncbi.nlm.nih.gov/10409727"
                }
            ],
            "uniprot_canonical_ac": "P03372-1"
        }
    ],
    "phosphorylation": [
        {
            "start_pos": 118,
            "end_pos": 118,
            "kinase_uniprot_canonical_ac": "P28482-1",
            "kinase_gene_name": "MAPK1",
            "residue": "Ser",
            "comment": "",
            "evidence": [
                {
                    "database": "iPTMnet",
                    "id": "P03372-1",
                    "url": "http://research.bioinformatics.udel.edu/iptmnet/entry/P03372-1"
                },
                {
                    "database": "PubMed",
                    "id": "10409727",
                    "url": "https://pubmed.ncbi.nlm.nih.gov/10409727"
                },
                {
                    "database": "PubMed",
                    "id": "12093745",
                    "url": "https://pubmed.ncbi.nlm.nih.gov/12093745"
                },
                {
                    "database": "PubMed",
                    "id": "9528769",
                    "url": "https://pubmed.ncbi.nlm.nih.gov/9528769"
                },
                {
                    "database": "iPTMnet",
                    "id": "P03372",
                    "url": "http://research.bioinformatics.udel.edu/iptmnet/entry/P03372"
                },
                {
                    "database": "PubMed",
                    "id": "7491495",
                    "url": "https://pubmed.ncbi.nlm.nih.gov/7491495"
                },
                {
                    "database": "phospho.ELM",
                    "id": "P03372",
                    "url": "http://phospho.elm.eu.org/byAccession/P03372.html"
                },
                {
                    "database": "PubMed",
                    "id": "15059947",
                    "url": "https://pubmed.ncbi.nlm.nih.gov/15059947"
                },
                {
                    "database": "PubMed",
                    "id": "12466266",
                    "url": "https://pubmed.ncbi.nlm.nih.gov/12466266"
                },
                {
                    "database": "PubMed",
                    "id": "17615152",
                    "url": "https://pubmed.ncbi.nlm.nih.gov/17615152"
                }
            ],
            "uniprot_canonical_ac": "P03372-1"
        }
    ],
    "record_id": "pubmed.10409727",
    "abstract": "The estrogen receptor (ER) regulates the expression of target genes in a ligand-dependent manner. The ligand-dependent activation function AF-2 of the ER is located in the ligand binding domain (LBD), while the N-terminal A/B domain (AF-1) functions in a ligand-independent manner when isolated from the LBD. AF-1 and AF-2 exhibit cell type and promoter context specificity. Furthermore, the AF-1 activity of the human ERalpha (hERalpha) is enhanced through phosphorylation of the Ser(118) residue by mitogen-activated protein kinase (MAPK). From MCF-7 cells, we purified and cloned a 68-kDa protein (p68) which interacted with the A/B domain but not with the LBD of hERalpha. Phosphorylation of hERalpha Ser(118) potentiated the interaction with p68. We demonstrate that p68 enhanced the activity of AF-1 but not AF-2 and the estrogen-induced as well as the anti-estrogen-induced transcriptional activity of the full-length ERalpha in a cell-type-specific manner. However, it did not potentiate AF-1 or AF-2 of ERbeta, androgen receptor, retinoic acid receptor alpha, or mineralocorticoid receptor. We also show that the RNA helicase activity previously ascribed to p68 is dispensable for the ERalpha AF-1 coactivator activity and that p68 binds to CBP in vitro. Furthermore, the interaction region for p68 in the ERalpha A/B domain was essential for the full activity of hERalpha AF-1. Taken together, these findings show that p68 acts as a coactivator specific for the ERalpha AF-1 and strongly suggest that the interaction between p68 and the hERalpha A/B domain is regulated by MAPK-induced phosphorylation of Ser(118).",
    "glycosylation": [],
    "snv": [],
    "glycation": []
}