{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T08:52:47Z","timestamp":1762505567775},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Syst Biol"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>The 250 kDa P2P-R protein (also known as PACT and Rbbp6) was cloned over a decade ago and was found to bind both the p53 and Rb1 tumor suppressor proteins. In addition, P2P-R has been associated with multiple biological functions, such as mitosis, mRNA processing, translation and ubiquitination. In the current studies, the online GeneNetwork system was employed to further probe P2P-R biological functions. Molecular studies were then performed to confirm the GeneNetwork evaluations.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>GeneNetwork and associated gene ontology links were used to investigate the coexpression of P2P-R with distinct functional sets of genes in an adipocyte genetic reference panel of HXB\/BXH recombinant strains of rats and an eye genetic reference panel of BXD recombinant inbred strains of mice. The results establish that biological networks of 75 and 135 transcription-associated gene products that include P2P-R are co-expressed in a genetically-defined manner in rat adipocytes and in the mouse eye, respectively. Of this large set of transcription-associated genes, &gt;10% are associated with hormone-mediated transcription. Since it has been previously reported that P2P-R can bind the SRC-1 transcription co-regulatory factor (steroid receptor co-activator 1, [Ncoa1]), the possible effects of P2P-R on estrogen-induced transcription were evaluated. Estrogen-induced transcription was repressed 50-70% by the transient transfection of P2P-R plasmid constructs into four different cell types. In addition, knockdown of P2P-R expression using an antisense oligonucleotide increased estrogen-mediated transcription. Co-immunoprecipitation assays confirmed that P2P-R interacts with SRC-1 and also demonstrated that P2P-R interacts with estrogen receptor \u03b1.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>The findings presented in this study provide strong support for the value of systems genetics, especially GeneNetwork, in discovering new functions of genes that can be confirmed by molecular analysis. More specifically, these data provide evidence that the expression of P2P-R co-varies in a genetically-defined manner with large transcription networks and that P2P-R can function as a co-repressor of estrogen-dependent transcription.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1752-0509-4-14","type":"journal-article","created":{"date-parts":[[2010,2,25]],"date-time":"2010-02-25T19:14:59Z","timestamp":1267125299000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Systems genetics analyses predict a transcription role for P2P-R: Molecular confirmation that P2P-R is a transcriptional co-repressor"],"prefix":"10.1186","volume":"4","author":[{"given":"Philippos","family":"Peidis","sequence":"first","affiliation":[]},{"given":"Thomas","family":"Giannakouros","sequence":"additional","affiliation":[]},{"given":"Matthew E","family":"Burow","sequence":"additional","affiliation":[]},{"given":"Robert W","family":"Williams","sequence":"additional","affiliation":[]},{"given":"Robert E","family":"Scott","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2010,2,25]]},"reference":[{"key":"403_CR1","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1007\/s00335-007-9040-6","volume":"18","author":"SK Sieberts","year":"2007","unstructured":"Sieberts SK, Schadt EE: Moving toward a system genetics view of disease. Mamm Genome. 2007, 18: 389-401. 10.1007\/s00335-007-9040-6","journal-title":"Mamm Genome"},{"key":"403_CR2","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1101\/gr.074914.107","volume":"18","author":"MP Keller","year":"2008","unstructured":"Keller MP, Choi Y, Wang P, Davis DB, Rabaglia ME, Oler AT, Stapleton DS, Argmann C, Schueler KL, Edwards S, Steinberg HA, Chaibub Neto E, Kleinhanz R, Turner S, Hellerstein MK, Schadt EE, Yandell BS, Kendziorski C, Attie AD: A gene expression network model of type 2 diabetes links cell cycle regulation in islets with diabetes susceptibility. Genome Res. 2008, 18: 706-716. 10.1101\/gr.074914.107","journal-title":"Genome Res"},{"key":"403_CR3","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1002\/jcp.20263","volume":"204","author":"RE Scott","year":"2005","unstructured":"Scott RE, White-Grindley E, Ruley HE, Chesler EJ, Williams RW: P2P-R expression is genetically coregulated with components of the translation machinery and with PUM2, a translational repressor that associates with P2P-R mRNA. J Cell Physiol. 2005, 204: 99-105. 10.1002\/jcp.20263","journal-title":"J Cell Physiol"},{"key":"403_CR4","doi-asserted-by":"publisher","first-page":"1212","DOI":"10.1073\/pnas.94.4.1212","volume":"94","author":"MM Witte","year":"1997","unstructured":"Witte MM, Scott RE: The proliferation potential protein-related (P2P-R) gene with domains encoding heterogeneous nuclear ribonucleoprotein association and Rb1 binding shows repressed expression during terminal differentiation. Proc Natl Acad Sci USA. 1997, 94: 1212-1217. 10.1073\/pnas.94.4.1212","journal-title":"Proc Natl Acad Sci USA"},{"key":"403_CR5","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1038\/sj.onc.1200825","volume":"14","author":"A Simons","year":"1997","unstructured":"Simons A, Melamed-Bessudo C, Wolkowicz R, Sperling J, Sperling R, Eisenbach L, Rotter V: Cloning and characterization of a cellular p53 binding protein that interacts with Rb. Oncogene. 1997, 14: 145-155. 10.1038\/sj.onc.1200825","journal-title":"Oncogene"},{"key":"403_CR6","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1038\/37297","volume":"390","author":"B Zhang","year":"1997","unstructured":"Zhang B, Gallegos M, Puoti A, Durkin E, Fields S, Kimble J, Wickens MP: A conserved RNA-binding protein that regulates sexual fates in the C. elegans hermaphrodite germ line. Nature. 1997, 390: 477-484. 10.1038\/37297","journal-title":"Nature"},{"key":"403_CR7","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1016\/S1097-2765(00)80085-4","volume":"1","author":"RP Wharton","year":"1998","unstructured":"Wharton RP, Sonoda J, Lee T, Patterson M, Murata Y: The Pumilio RNA-binding domain is also a translational regulator. Mol Cell. 1998, 1: 863-872. 10.1016\/S1097-2765(00)80085-4","journal-title":"Mol Cell"},{"key":"403_CR8","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1002\/jcp.10163","volume":"193","author":"S Gao","year":"2002","unstructured":"Gao S, Scott RE: P2P-R protein overexpression restricts mitotic progression at prometaphase and promotes mitotic apoptosis. J Cell Physiol. 2002, 193: 199-207. 10.1002\/jcp.10163","journal-title":"J Cell Physiol"},{"key":"403_CR9","first-page":"3837","volume":"22","author":"RE Scott","year":"2002","unstructured":"Scott RE, Gao S: P2P-R deficiency modifies nocodazole-induced mitotic arrest and UV-induced apoptosis. Anticancer Res. 2002, 22: 3837-3842.","journal-title":"Anticancer Res"},{"key":"403_CR10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1472-6807-6-1","volume":"6","author":"DJ Pugh","year":"2006","unstructured":"Pugh DJ, Ab E, Faro A, Lutya PT, Hoffmann E, Rees DJ: DWNN, a novel ubiquitin-like domain, implicates RBBP6 in mRNA processing and ubiquitin-like pathways. BMC Struct Biol. 2006, 6: 1- 10.1186\/1472-6807-6-1","journal-title":"BMC Struct Biol"},{"key":"403_CR11","doi-asserted-by":"publisher","first-page":"7951","DOI":"10.1073\/pnas.0701916104","volume":"104","author":"L Li","year":"2007","unstructured":"Li L, Deng B, Xing G, Teng Y, Tian C, Cheng X, Yin X, Yang J, Gao X, Zhu Y, Sun Q, Zhang L, Yang X, He F: PACT is a negative regulator of p53 and essential for cell growth and embryonic development. Proc Natl Acad Sci USA. 2007, 104: 7951-7856. 10.1073\/pnas.0701916104","journal-title":"Proc Natl Acad Sci USA"},{"key":"403_CR12","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1016\/j.jmb.2008.09.060","volume":"384","author":"M Chibi","year":"2008","unstructured":"Chibi M, Meyer M, Skepu A, G Rees DJ, Moolman-Smook JC, Pugh DJ: RBBP6 interacts with multifunctional protein YB-1 through its RING finger domain leading to ubiquitination and proteasomal degradation of YB-1. J Mol Biol. 2008, 384: 908-916. 10.1016\/j.jmb.2008.09.060","journal-title":"J Mol Biol"},{"key":"403_CR13","doi-asserted-by":"publisher","first-page":"6437","DOI":"10.1158\/1078-0432.CCR-04-0841","volume":"10","author":"Y Yoshitake","year":"2004","unstructured":"Yoshitake Y, Nakatsura T, Monji M, Senju S, Matsuyoshi H, Tsukamoto H, Hosaka S, Komori H, Fukuma D, Ikuta Y, Katagiri T, Furukawa Y, Ito H, Shinohara M, Nakamura Y, Nishimura Y: Proliferation potential-related protein, an ideal esophageal cancer antigen for immunotherapy, identified using complementary DNA microarray analysis. Clin Cancer. 2004, 10: 6437-6448. 10.1158\/1078-0432.CCR-04-0841.","journal-title":"Clin Cancer"},{"key":"403_CR14","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1038\/ng1522","volume":"37","author":"N H\u00fcbner","year":"2005","unstructured":"H\u00fcbner N, Wallace CA, Zimdahl H, Petretto E, Schulz H, Maciver F, Mueller M, Hummel O, Monti J, Zidek V, Musilova A, Kren V, Causton H, Game L, Born G, Schmidt S, Muller A, Cook SA, Kurtz TW, Whittaker J, Pravenec M, Aitman TJ: Integrated transcriptional profiling and linkage analysis for identification of genes underlying disease. Nature Genetics. 2005, 37: 243-253. 10.1038\/ng1522","journal-title":"Nature Genetics"},{"key":"403_CR15","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1093\/bioinformatics\/btg410","volume":"20","author":"LM Cope","year":"2003","unstructured":"Cope LM, Irizarry RA, Jaffee H, Wu Z, Speed TP: A benchmark for Affymetrix genechip expression measures. Bioinformatics. 2003, 20: 323-331. 10.1093\/bioinformatics\/btg410.","journal-title":"Bioinformatics"},{"key":"403_CR16","first-page":"1730","volume":"15","author":"EE Geisert","year":"2009","unstructured":"Geisert EE, Lu L, Freeman-Anderson ME, Wang X, Gu W, Jiao Y, Williams RW: Gene expression landscape of the mammalian eye: A global survey anddatabase of mRNAs of 103 strains of mice. Molecular Vision. 2009, 15: 1730-1763.","journal-title":"Molecular Vision"},{"key":"403_CR17","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1210\/er.2004-0018","volume":"26","author":"RC Wu","year":"2005","unstructured":"Wu RC, Smith CL, O'Malley BW: Transcriptional regulation by steroid receptor coactivator phosphorylation. Endocr Rev. 2005, 26: 393-399. 10.1210\/er.2004-0018","journal-title":"Endocr Rev"},{"key":"403_CR18","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1002\/jcp.10381","volume":"197","author":"S Gao","year":"2003","unstructured":"Gao S, Scott RE: Stable overexpression of specific segments of the P2P-R protein in human MCF-7 cells promotes camptothecin-induced apoptosis. J Cell Physiol. 2003, 197: 445-452. 10.1002\/jcp.10381","journal-title":"J Cell Physiol"},{"key":"403_CR19","doi-asserted-by":"publisher","first-page":"2836","DOI":"10.1073\/pnas.050580997","volume":"97","author":"G Poelzl","year":"2000","unstructured":"Poelzl G, Kasai Y, Mochizuki N, Shaul PW, Brown M, Mendelsohn ME: Specific association of estrogen receptor beta with the cell cycle spindle assembly checkpoint protein, MAD2. Proc Natl Acad Sci USA. 2000, 97: 2836-2839. 10.1073\/pnas.050580997","journal-title":"Proc Natl Acad Sci USA"},{"key":"403_CR20","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1038\/35050515","volume":"3","author":"DL Stenoien","year":"2001","unstructured":"Stenoien DL, Patel K, Mancini MG, Dutertre M, O'Malley BW, Mancini MA: FRAP reveals that mobility of oestrogen receptor-alpha is ligand- and proteasome-dependent. Nature Cell Biol. 2001, 3: 15-23. 10.1038\/35050515","journal-title":"Nature Cell Biol"},{"key":"403_CR21","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1093\/nar\/24.5.843","volume":"24","author":"A Renz","year":"1996","unstructured":"Renz A, Fackelmayer FO: Purification and molecular cloning of the scaffold attachment factor B (SAF-B), a novel human nuclear protein that specifically binds to S\/MAR-DNA. Nucl Acids Res. 1996, 24: 843-849. 10.1093\/nar\/24.5.843","journal-title":"Nucl Acids Res"},{"key":"403_CR22","doi-asserted-by":"publisher","first-page":"3542","DOI":"10.1093\/nar\/26.15.3542","volume":"26","author":"O Nayler","year":"1998","unstructured":"Nayler O, Stratling W, Bourquin J, Stagljar I, Lindemann L, Jasper H, Hartmann AM, Fackelmayer FO, Ullrich A, Stamm S: SAF-B protein couples transcription and pre-mRNA splicing to SAR\/MAR elements. Nucl Acids Res. 1998, 26: 3542-3549. 10.1093\/nar\/26.15.3542","journal-title":"Nucl Acids Res"},{"key":"403_CR23","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1210\/mend.14.3.0432","volume":"14","author":"S Oesterreich","year":"2000","unstructured":"Oesterreich S, Zhang Q, Hopp T, Fuqua SAW, Michaelis M, Zhao HH, Davie JR, Osborne CK, Lee AV: Tamoxifen-bound estrogen receptor (ER) strongly interacts with the nuclear matrix protein HET\/SAF-B, a novel inhibitor of ER-mediated transactivation. Mol Endocrinol. 2000, 14: 369-381. 10.1210\/me.14.3.369","journal-title":"Mol Endocrinol"},{"key":"403_CR24","doi-asserted-by":"publisher","first-page":"20059","DOI":"10.1074\/jbc.M212988200","volume":"278","author":"SM Townson","year":"2003","unstructured":"Townson SM, Dobrzycka KM, Lee AV, Air M, Deng W, Kang K, Jiang S, Kioka N, Michaelis K, Oesterreich S: SAF-B2, a new scaffold attachment factor homolog and estrogen receptor corepressor. J Biol Chem. 2003, 278: 20059-20068. 10.1074\/jbc.M212988200","journal-title":"J Biol Chem"},{"key":"403_CR25","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1002\/jcb.10685","volume":"90","author":"S Oesterreich","year":"2003","unstructured":"Oesterreich S: Scaffold attachment factors SAFB1 and SAFB2: Innocent bystanders or critical players in breast tumorigenesis?. J Cell Biochem. 2003, 90: 653-661. 10.1002\/jcb.10685","journal-title":"J Cell Biochem"},{"key":"403_CR26","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1002\/jcb.10618","volume":"90","author":"RE Scott","year":"2003","unstructured":"Scott RE, Giannakouros T, Gao S, Peidis P: Functional potential of P2P-R: A role in the cell cycle and cell differentiation related to its interactions with proteins that bind to matrix associated regions of DNA. J Cell Biochem. 2003, 90: 6-12. 10.1002\/jcb.10618","journal-title":"J Cell Biochem"},{"key":"403_CR27","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1385\/NI:1:4:343","volume":"1","author":"EJ Chesler","year":"2003","unstructured":"Chesler EJ, Wang J, Lu L, Qu Y, Manly KF, Williams RW: Genetic correlates of gene expression in recombinant inbred strains. Neuroinformatics. 2003, 1: 343-358. 10.1385\/NI:1:4:343","journal-title":"Neuroinformatics"},{"key":"403_CR28","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1385\/NI:1:4:299","volume":"1","author":"J Wang","year":"2003","unstructured":"Wang J, Williams RW, Manly KF: WebQTL: Web-based complex trait analysis. Neuroinformatics. 2003, 1: 299-308. 10.1385\/NI:1:4:299","journal-title":"Neuroinformatics"},{"key":"403_CR29","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/1471-2105-5-16","volume":"5","author":"B Zhang","year":"2004","unstructured":"Zhang B, Schmoyer D, Kirov S, Snoddy J: GOTree Machine (GOTM): a web-based platform for interpreting sets of interesting genes using Gene Ontology hierarchies. BMC Bioinformatics. 2004, 5: 16- 10.1186\/1471-2105-5-16","journal-title":"BMC Bioinformatics"},{"key":"403_CR30","doi-asserted-by":"publisher","first-page":"1750","DOI":"10.1210\/jc.86.4.1750","volume":"86","author":"ME Burow","year":"2001","unstructured":"Burow ME, Boue SM, Collins-Burow BM, Melnik LI, Doung BN, Carter-Wientjes CHC, Li S, Wiese TE, Cleveland TE, McLachlan JA: Phytochemical glyceollins, isolated from soy, mediate antihormone effects through estrogen alpha and beta. J Clin Endocrin Metabol. 2001, 86: 1750-1758. 10.1210\/jc.86.4.1750.","journal-title":"J Clin Endocrin Metabol"}],"container-title":["BMC Systems Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1752-0509-4-14.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T04:56:47Z","timestamp":1630472207000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcsystbiol.biomedcentral.com\/articles\/10.1186\/1752-0509-4-14"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,2,25]]},"references-count":30,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2010,12]]}},"alternative-id":["403"],"URL":"https:\/\/doi.org\/10.1186\/1752-0509-4-14","relation":{},"ISSN":["1752-0509"],"issn-type":[{"value":"1752-0509","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,2,25]]},"assertion":[{"value":"7 May 2009","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 February 2010","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 February 2010","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"14"}}