{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:55:08Z","timestamp":1790009708532,"version":"4.0.1"},"reference-count":33,"publisher":"The Endocrine Society","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,7,1]]},"abstract":"<jats:p>B-cell lymphoma 2 (BCL2) family kin (BFK) is a recently identified novel protein that is similar to proteins of the BCL2 family. In the present study, we discovered that the mouse Bfk transcript is expressed at the highest level in the epididymis. Two transcripts of 0.9 and 2.6 kb in size were identified, with alternative exon 4 structures, resulting in a difference in the last three to five amino acids of the variants. However, the 0.9-kb transcript was found to be the predominant form in the epididymis and mammary gland, another tissue with strong Bfk expression. Epididymal Bfk expression was regulated both by androgens and other testicular factors. It is thus one of the few initial-segment enriched genes under androgen control, the majority of them being regulated by other testicular factors. BFK protein was expressed specifically in the principal cells of the epididymis. Its nuclear localization was evident in the initial segment and caput epididymis and in the epithelium of pregnant female mammary gland. The expression of BFK-enhanced green fluorescent protein recombinant protein in epididymal cells further confirmed the predominant nuclear localization of BFK with nucleo-cytoplasmic shuttling. Overexpressing BFK in epididymal cells did not induce apoptosis. However, enhanced caspase 3 activation was observed in the presence of BFK upon staurosporine-induced apoptosis. This suggests that BFK may have a proapoptotic role only after the process has been initiated by other mechanisms. Being exceptionally highly expressed in the initial segment, Bfk is suggested to have a role in the differentiation of this segment of the epididymis.<\/jats:p>","DOI":"10.1210\/en.2007-0018","type":"journal-article","created":{"date-parts":[[2007,4,6]],"date-time":"2007-04-06T00:44:27Z","timestamp":1175820267000},"page":"3196-3204","source":"Crossref","is-referenced-by-count":17,"title":["Bfk, a Novel Member of the Bcl2 Gene Family, Is Highly Expressed in Principal Cells of the Mouse Epididymis and Demonstrates a Predominant Nuclear Localization"],"prefix":"10.1210","volume":"148","author":[{"given":"Dwi Ari","family":"Pujianto","sequence":"first","affiliation":[{"name":"Department of Physiology (D.A.P., A.E.D., P.S., J.J., I.H., M.P.), Institute of Biomedicine, University of Turku, 20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasios E.","family":"Damdimopoulos","sequence":"additional","affiliation":[{"name":"Department of Physiology (D.A.P., A.E.D., P.S., J.J., I.H., M.P.), Institute of Biomedicine, University of Turku, 20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Sipila\u0308","sequence":"additional","affiliation":[{"name":"Department of Physiology (D.A.P., A.E.D., P.S., J.J., I.H., M.P.), Institute of Biomedicine, University of Turku, 20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenni","family":"Jalkanen","sequence":"additional","affiliation":[{"name":"Department of Physiology (D.A.P., A.E.D., P.S., J.J., I.H., M.P.), Institute of Biomedicine, University of Turku, 20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilpo","family":"Huhtaniemi","sequence":"additional","affiliation":[{"name":"Department of Physiology (D.A.P., A.E.D., P.S., J.J., I.H., M.P.), Institute of Biomedicine, University of Turku, 20520 Turku, Finland"},{"name":"Department of Reproductive Biology (I.H.), Imperial College London, Hammersmith Campus, London W12 0NN, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matti","family":"Poutanen","sequence":"additional","affiliation":[{"name":"Department of Physiology (D.A.P., A.E.D., P.S., J.J., I.H., M.P.), Institute of Biomedicine, University of Turku, 20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071613281451100_R1","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1210\/endo.142.3.8045","article-title":"Gene duplication gives rise to a new 17-kilodalton lipocalin that shows epididymal region-specific expression and testicular factor(s) regulation.","volume":"142","author":"Lareyre","year":"2001","journal-title":"Endocrinology"},{"key":"2020071613281451100_R2","first-page":"1653","article-title":"The CRES gene: a unique testis-regulated gene related to the cystatin family is highly restricted in its expression to the proximal region of the mouse epididymis.","volume":"6","author":"Cornwall","year":"1992","journal-title":"Mol Endocrinol"},{"key":"2020071613281451100_R3","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1101\/gad.6.3.481","article-title":"Molecular cloning and characterization of PEA3, a new member of the Ets oncogene family that is differentially expressed in mouse embryonic cells.","volume":"6","author":"Xin","year":"1992","journal-title":"Genes Dev"},{"key":"2020071613281451100_R4","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1677\/jme.0.0040005","article-title":"Molecular cloning of a cDNA for androgen-regulated proteins secreted by the mouse epididymis.","volume":"4","author":"Ghyselinck","year":"1990","journal-title":"J Mol Endocrinol"},{"key":"2020071613281451100_R5","doi-asserted-by":"crossref","first-page":"2971","DOI":"10.1210\/endo.139.6.6074","article-title":"Molecular cloning and hormonal regulation of a murine epididymal retinoic acid-binding protein messenger ribonucleic acid.","volume":"139","author":"Lareyre","year":"1998","journal-title":"Endocrinology"},{"key":"2020071613281451100_R6","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1101\/gad.10.10.1184","article-title":"The c-ros tyrosine kinase receptor controls regionalization and differentiation of epithelial cells in the epididymis.","volume":"10","author":"Sonnenberg-Riethmacher","year":"1996","journal-title":"Genes Dev"},{"key":"2020071613281451100_R7","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1002\/mrd.1080420205","article-title":"Mouse androgen-dependent epididymal glycoprotein CRISP-1 (DE\/AEG): isolation, biochemical characterization, and expression in recombinant form.","volume":"42","author":"Eberspaecher","year":"1995","journal-title":"Mol Reprod Dev"},{"key":"2020071613281451100_R8","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1002\/j.1939-4640.1999.tb03374.x","article-title":"Changes in the number, proliferation rates, and bcl-2 protein immunoexpression of epithelial and periductal cells from rat epididymis during postnatal development.","volume":"20","author":"Ramirez","year":"1999","journal-title":"J Androl"},{"key":"2020071613281451100_R9","doi-asserted-by":"crossref","first-page":"17323","DOI":"10.1016\/S0021-9258(17)44906-4","article-title":"Activation of internucleosomal DNA cleavage in human CEM lymphocytes by glucocorticoid and novobiocin. Evidence for a non-Ca2(+)-requiring mechanism(s).","volume":"265","author":"Alnemri","year":"1990","journal-title":"J Biol Chem"},{"key":"2020071613281451100_R10","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/BF00048058","article-title":"A biochemical hallmark of apoptosis: internucleosomal degradation of the genome.","volume":"11","author":"Compton","year":"1992","journal-title":"Cancer Metastasis Rev"},{"key":"2020071613281451100_R11","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1006\/smim.1996.0052","article-title":"The role of the Bcl-2 family of apoptosis regulatory proteins in the immune system.","volume":"9","author":"Hawkins","year":"1997","journal-title":"Semin Immunol"},{"key":"2020071613281451100_R12","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/284555a0","article-title":"Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation.","volume":"284","author":"Wyllie","year":"1980","journal-title":"Nature"},{"key":"2020071613281451100_R13","doi-asserted-by":"crossref","first-page":"5497","DOI":"10.1210\/endo.138.12.5588","article-title":"Expression and function of a proapoptotic Bcl-2 family member Bcl-XL\/Bcl-2-associated death promoter (BAD) in rat ovary.","volume":"138","author":"Kaipia","year":"1997","journal-title":"Endocrinology"},{"key":"2020071613281451100_R14","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1006\/dbio.2001.0445","article-title":"BCLW mediates survival of postmitotic Sertoli cells by regulating BAX activity.","volume":"239","author":"Ross","year":"2001","journal-title":"Dev Biol"},{"key":"2020071613281451100_R15","doi-asserted-by":"crossref","first-page":"2262","DOI":"10.1093\/emboj\/16.9.2262","article-title":"An early and massive wave of germinal cell apoptosis is required for the development of functional spermatogenesis.","volume":"16","author":"Rodriguez","year":"1997","journal-title":"EMBO J"},{"key":"2020071613281451100_R16","first-page":"31","article-title":"Down regulation of Bcl-2 is the first step on Fas-mediated apoptosis of male reproductive tract.","volume":"13","author":"Suzuki","year":"1996","journal-title":"Oncogene"},{"key":"2020071613281451100_R17","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1095\/biolreprod67.4.1189","article-title":"Abdominal temperature induces region-specific p53-independent apoptosis in the cauda epididymidis of the mouse.","volume":"67","author":"Jara","year":"2002","journal-title":"Biol Reprod"},{"key":"2020071613281451100_R18","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/sj.cdd.4401204","article-title":"Bfk: a novel weakly proapoptotic member of the Bcl-2 protein family with a BH3 and a BH2 region.","volume":"10","author":"Coultas","year":"2003","journal-title":"Cell Death Differ"},{"key":"2020071613281451100_R19","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1101\/gad.897601","article-title":"BH3-only proteins that bind pro-survival Bcl-2 family members fail to induce apoptosis in the absence of Bax and Bak.","volume":"15","author":"Zong","year":"2001","journal-title":"Genes Dev"},{"key":"2020071613281451100_R20","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/S1097-2765(01)00320-3","article-title":"BCL-2, BCL-XL sequester BH3 domain-only molecules preventing BAX- and BAK-mediated mitochondrial apoptosis.","volume":"8","author":"Cheng","year":"2001","journal-title":"Mol Cell"},{"key":"2020071613281451100_R21","doi-asserted-by":"crossref","first-page":"3646","DOI":"10.1016\/j.febslet.2005.05.050","article-title":"Expression of pro-apoptotic Bfk isoforms reduces during malignant transformation in the human gastrointestinal tract.","volume":"579","author":"Dempsey","year":"2005","journal-title":"FEBS Lett"},{"key":"2020071613281451100_R22","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1095\/biolreprod.105.047811","article-title":"Differential endocrine regulation of genes enriched in initial segment and distal caput of the mouse epididymis as revealed by genome-wide expression profiling.","volume":"75","author":"Sipila","year":"2006","journal-title":"Biol Reprod"},{"key":"2020071613281451100_R23","author":"Ausubel","year":"1995"},{"key":"2020071613281451100_R24","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1210\/en.2003-0831","article-title":"Immortalization of epididymal epithelium in transgenic mice expressing simian virus 40 T antigen: characterization of cell lines and regulation of the polyoma enhancer activator 3.","volume":"145","author":"Sipila","year":"2004","journal-title":"Endocrinology"},{"key":"2020071613281451100_R25","doi-asserted-by":"crossref","first-page":"4637","DOI":"10.1210\/en.2003-0404","article-title":"Proteomic profiling of epididymis and vas deferens: identification of proteins regulated during rat genital tract development.","volume":"144","author":"Umar","year":"2003","journal-title":"Endocrinology"},{"key":"2020071613281451100_R26","doi-asserted-by":"crossref","first-page":"8662","DOI":"10.1073\/pnas.161506698","article-title":"Ubiquitin-protein ligase activity of X-linked inhibitor of apoptosis protein promotes proteasomal degradation of caspase-3 and enhances its anti-apoptotic effect in Fas-induced cell death.","volume":"98","author":"Suzuki","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071613281451100_R27","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1128\/MCB.22.3.816-834.2002","article-title":"Hsp27 as a negative regulator of cytochrome C release.","volume":"22","author":"Paul","year":"2002","journal-title":"Mol Cell Biol"},{"key":"2020071613281451100_R28","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0014-5793(03)00180-7","article-title":"C-terminal 15 kDa fragment of cytoskeletal actin is posttranslationally N-myristoylated upon caspase-mediated cleavage and targeted to mitochondria.","volume":"539","author":"Utsumi","year":"2003","journal-title":"FEBS Lett"},{"key":"2020071613281451100_R29","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.1073\/pnas.93.5.2234","article-title":"Cleavage of actin by interleukin 1\u03b2-converting enzyme to reverse DNase I inhibition.","volume":"93","author":"Kayalar","year":"1996","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071613281451100_R30","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.1038\/sj.onc.1202558","article-title":"Caspase-mediated cleavage of cytoskeletal actin plays a positive role in the process of morphological apoptosis.","volume":"18","author":"Mashima","year":"1999","journal-title":"Oncogene"},{"key":"2020071613281451100_R31","doi-asserted-by":"crossref","first-page":"5087","DOI":"10.1038\/sj.onc.1204662","article-title":"The growth-promoting activity of the Bad protein in chicken embryo fibroblasts requires binding to protein 14-3-3.","volume":"20","author":"Maslyar","year":"2001","journal-title":"Oncogene"},{"key":"2020071613281451100_R32","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/S0046-8177(96)90362-7","article-title":"bcl-2: role in epithelial differentiation and oncogenesis.","volume":"27","author":"Lu","year":"1996","journal-title":"Hum Pathol"},{"key":"2020071613281451100_R33","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1210\/en.2002-220705","article-title":"Gene expression is differentially regulated in the epididymis after orchidectomy.","volume":"144","author":"Ezer","year":"2003","journal-title":"Endocrinology"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/148\/7\/3196\/10724955\/endo3196.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/148\/7\/3196\/10724955\/endo3196.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,13]],"date-time":"2024-02-13T00:43:35Z","timestamp":1707785015000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/148\/7\/3196\/2501930"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,7,1]]},"references-count":33,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2007,7,1]]}},"URL":"https:\/\/doi.org\/10.1210\/en.2007-0018","relation":{},"ISSN":["0013-7227","1945-7170"],"issn-type":[{"value":"0013-7227","type":"print"},{"value":"1945-7170","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,7,1]]}}}