{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:01:43Z","timestamp":1789430503180,"version":"build-2803163510"},"reference-count":48,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,6,3]],"date-time":"2023-06-03T00:00:00Z","timestamp":1685750400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Scientific Research Projects Unit of Tokat Gaziosmanpasa University","award":["2015\/110"],"award-info":[{"award-number":["2015\/110"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: The ubiquitin proteosome system (UPS) is a non-lysosomal pathway that functions in all eukaryotes. The transport of polyubiquitinated proteins to proteosomes takes place via the p97\/Valosin-containing protein (VCP) chaperone protein. The p97\/VCP binds to polyubiquitinated proteins, allowing these proteins to reach the proteasome and, thus, their destruction. In the case of p97\/VCP deficiency, ubiquitinated proteins accumulate in the cell cytoplasm, and their subsequent failure to break down produces various pathological conditions. Small VCP interacting protein (SVIP) and p97\/VCP proteins have not been studied in human testicular tissues from different postnatal periods. Therefore, in our study, we aimed to examine the expression of SVIP and p97\/VCP in postnatal human testicular tissues. Our study aimed to contribute to further studies on the use of these proteins as testicular cell biomarkers in cases of unexplained male infertility. Materials and Methods: Immunohistochemical studies with the aim of determining the expression of p97\/VCP and SVIP proteins in neonatal, prepubertal, pubertal, adult, and geriatric human testis tissues were performed. Results: In testicular sections obtained from a neonatal group, p97\/VCP and SVIP were localized in different testicular and interstitial cells, and the lowest expression was observed in this group. While the expressions of these proteins were low in the neonatal period, they increased gradually in the prepubertal, pubertal and adult periods. The expression of p97\/VCP and SVIP, which peaked in adulthood, showed a significant decrease in the geriatric period. Conclusions: As a result, the expression of p97\/VCP and SVIP correlated with the increase in age, but it decreased significantly in older groups.<\/jats:p>","DOI":"10.3390\/medicina59061079","type":"journal-article","created":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T01:53:25Z","timestamp":1685930005000},"page":"1079","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Determination of p97\/VCP (Valosin Containing Protein) and SVIP (Small VCP Interacting Protein) Expression Patterns in Human Testis"],"prefix":"10.3390","volume":"59","author":[{"given":"Akg\u00fcl","family":"Ar\u0131c\u0131","sequence":"first","affiliation":[{"name":"Department of Medical Pathology, Tokat Gaziosmanpasa University, 60100 Tokat, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fikret","family":"Erdemir","sequence":"additional","affiliation":[{"name":"Department of Urology, Tokat Gaziosmanpasa University, 60100 Tokat, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/BF02705243","article-title":"The ubiquitin-proteasome system","volume":"31","author":"Nandi","year":"2006","journal-title":"J. Biosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.tcb.2013.12.003","article-title":"Perilous journey: A tour of the ubiquitin-proteasome system","volume":"24","author":"Kleiger","year":"2014","journal-title":"Trends Cell Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/j.tibs.2017.09.002","article-title":"The ubiquitin code in the ubiquitin-proteasome system and autophagy","volume":"42","author":"Kwon","year":"2017","journal-title":"Tends Biochem. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1152\/physrev.00027.2001","article-title":"The ubiquitin-proteasome proteolytic pathway: Destruction for the sake of construction","volume":"82","author":"Glickman","year":"2002","journal-title":"Physiol. Rev."},{"key":"ref_5","first-page":"3877","article-title":"The VCP\/p97 system at glance: Connecting cellular function to disease pathogenesis","volume":"127","author":"Meyer","year":"2014","journal-title":"J. Cell Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/ncb2407","article-title":"Emerging functions of the VCP\/p97 AAA-ATPase in the ubiquitin system","volume":"14","author":"Meyer","year":"2012","journal-title":"Nat. Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2578","DOI":"10.1016\/j.febslet.2015.08.028","article-title":"Control of p97 function by cofactor binding","volume":"589","author":"Buchberger","year":"2015","journal-title":"FEEBS Lett."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Costantini, S., Capone, F., Polo, A., Bagnara, P., and Budillon, A. (2021). Valosin-containing protein (VCP)\/p97: A prognostik biomarker and therapeutic target in cancer. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221810177"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.bbamcr.2011.07.001","article-title":"Recent advances in p97\/VCP\/Cdc48 cellular functions","volume":"1823","author":"Yamanaka","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"39","DOI":"10.3389\/fmolb.2017.00039","article-title":"A mighty \u201cprotein extractor\u201d of the cell: Structure and function of the p97\/CDC48 ATPase","volume":"4","author":"Ye","year":"2017","journal-title":"Front. Mol. Biosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"9159","DOI":"10.1007\/s11033-022-07740-3","article-title":"The determination of the relationship between p97\/VCP, small VCP-interacting protein, two ERAD proteins and steroidogenesis in Leydig cell lines","volume":"49","author":"Akcan","year":"2022","journal-title":"Mol. Biol. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"33908","DOI":"10.1074\/jbc.M704446200","article-title":"Identification of SVIP as an endogenous inhibitor of endoplasmic reticulum-associated degradation","volume":"282","author":"Ballar","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"35359","DOI":"10.1074\/jbc.M603355200","article-title":"The role of a novel p97\/valosin-containing protein-interacting motif of gp78 in endoplasmic reticulum-associated degradation","volume":"281","author":"Ballar","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"38670","DOI":"10.1074\/jbc.M111.274472","article-title":"The general definition of the p97\/valosin-containing protein (VCP)-interacting motif (VIM) delineates a new family of p97 cofactors","volume":"286","author":"Stapf","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.bbrc.2013.09.056","article-title":"Structure and expression of a novel compact myelin protein-small VCP-interacting protein (SVIP)","volume":"440","author":"Wu","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/1477-7827-9-117","article-title":"Developmental expression of p97\/VCP (Valosin-containing protein) and Jab1\/CSN5 in the rat testis and epididymis","volume":"9","author":"Cayli","year":"2011","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1177\/1933719111417886","article-title":"Interaction between Smad1 and p97\/VCP in rat testis and epididymis during the postnatal development","volume":"19","author":"Cayli","year":"2012","journal-title":"Reprod. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1093\/genetics\/100.4.547","article-title":"Cold-sensitive cell-division-cycle mutants of yeast: Isolation, properties, and pseudoreversion studies","volume":"100","author":"Moir","year":"1982","journal-title":"Genetics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1038\/35087056","article-title":"Valosin-containing protein is a multi-ubiquitin chain-targeting factor required in ubiquitin-proteasome degradation","volume":"3","author":"Dai","year":"2001","journal-title":"Nat. Cell Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1093\/hmg\/ddr612","article-title":"Altered intracellular localization and valosin-containing protein (p97 VCP) interaction underlie ATP7A-related distal motor neuropathy","volume":"21","author":"Yi","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1038\/sj.cdd.4400907","article-title":"VCP\/p97 in abnormal protein aggregates, cytoplasmic vacuoles, and cell death, phenotypes relevant to neurodegeneration","volume":"8","author":"Hirabayashi","year":"2001","journal-title":"Cell Death Differ."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1007\/s00109-011-0732-8","article-title":"Critical role of proteostasis-imbalance in pathogenesis of COPD and severe emphysema","volume":"89","author":"Min","year":"2011","journal-title":"J. Mol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2511","DOI":"10.1111\/j.1582-4934.2008.00462.x","article-title":"AAA ATPase p97\/VCP: Cellular functions, disease and therapeutic potential","volume":"12","author":"Vij","year":"2008","journal-title":"J. Cell Mol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"9919","DOI":"10.1007\/s13277-015-3748-9","article-title":"High expression of valosin-vontaining protein predicts poor prognosis in patients with breast carcinoma","volume":"36","author":"Cui","year":"2015","journal-title":"Tumor Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1158\/1078-0432.CCR-1576-03","article-title":"Expression of valosin-containing protein in colorectal Carcinomas as a predictor for disease recurrence and prognosis","volume":"10","author":"Yamamoto","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1245\/ASO.2005.07.002","article-title":"Increased expression of valosin-containing protein (p97) is correlated with disease recurrence in follicular thyroid cancer","volume":"12","author":"Yamamoto","year":"2005","journal-title":"Ann. Surg. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1091\/mbc.02-07-0115","article-title":"SVIP is a novel VCP\/p97-interacting protein whose expression causes cell vacuolation","volume":"14","author":"Nagahama","year":"2003","journal-title":"Mol. Biol. Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1530\/rep.1.01075","article-title":"All in the family: TGF-\u03b2 family action in testis development","volume":"132","author":"Itman","year":"2006","journal-title":"Reproduction"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.semcdb.2014.03.007","article-title":"Regulation of spermatogenesis: An evolutionary biologist\u2019s perspective","volume":"29","author":"Schlatt","year":"2014","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.ydbio.2010.03.007","article-title":"TGF\u03b2 signaling in male germ cells regulates gonocyte quiescence and fertility in mice","volume":"342","author":"Moreno","year":"2010","journal-title":"Dev. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.semcdb.2014.04.007","article-title":"The roles and regulation of Sertoli cells in fate determinations of spermatogonial stem cells and spermatogenesis","volume":"29","author":"Hai","year":"2014","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Horibe, A., Eid, N., Ito, Y., Otsuki, Y., and Kondo, Y. (2019). Thanol-induced autophagy in Sertoli cells is specifially marked at androgen-dependent stages of the spermatogenic cycle: Potential mechanisms and implications. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20010184"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"570","DOI":"10.4103\/aja.aja_12_19","article-title":"Autophagy is increased in cryptorchid testis resulting in abnormal spermatozoa","volume":"21","author":"Yefimova","year":"2019","journal-title":"Asian J. Androl."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.theriogenology.2020.09.017","article-title":"Inhibition of p97\/VCP function leads to defective autophagosome maturation, cell cycle arrest and apoptosis in mouse Sertoli cells","volume":"158","author":"Cayli","year":"2020","journal-title":"Theriogenology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.placenta.2018.05.013","article-title":"Altered expression of p97\/Valosin containing protein and impaired autophagy in preeclamptic human placenta","volume":"67","author":"Ozsoy","year":"2018","journal-title":"Placenta"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1126\/science.278.5337.419","article-title":"The endocrinology of aging","volume":"278","author":"Lamberts","year":"1997","journal-title":"Science"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Romanuik, T.L., Wang, G., Holt, R.A., Jones, S.J.M., Marra, M.A., and Sadar, M.D. (2009). Identification of novel androgen-responsive genes by sequencing of longSAGE libraries. BMC Genom., 10.","DOI":"10.1186\/1471-2164-10-476"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"40719","DOI":"10.1038\/srep40719","article-title":"Androgen mediated regulation of endoplaplazmic reticulum-associated degradation and its effects on prostate cancer","volume":"7","author":"Erzurumlu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"23142","DOI":"10.18632\/oncotarget.15509","article-title":"Regulation of p53 glioma cell proliferation by androgen receptor-mediated inhibition of small VCP\/p97-interacting protein expression","volume":"8","author":"Bao","year":"2017","journal-title":"Oncotarget"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"6876","DOI":"10.1073\/pnas.0307306101","article-title":"Infertility with defective spermatogenesis and hypotestostronemia in male mice lacking the androgen receptor in Sertoli cells","volume":"101","author":"Chang","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.yexcr.2015.11.024","article-title":"Lipid droplets and steroidogenic cells","volume":"340","author":"Shen","year":"2016","journal-title":"Exp. Cell Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.repbio.2020.01.006","article-title":"Analysis of the developmental expression of small VCP-interacting protein and its interaction with steroidogenic acute regulatory protein in Leydig cells","volume":"20","author":"Akcan","year":"2020","journal-title":"Reprod. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"12070","DOI":"10.1038\/srep12070","article-title":"Proteomic analysis of murine testes lipid droplets","volume":"5","author":"Wang","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"441","DOI":"10.14348\/molcells.2017.0115","article-title":"Crosstalk and interplay between the ubiquitin-proteasome system and autophagy","volume":"40","author":"Ji","year":"2017","journal-title":"Mol. Cells"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4834","DOI":"10.1073\/pnas.1015312108","article-title":"Reversible inhibit\u00f6r of p97, DBeQ, impairs both ubiquitin-dependent and autophagic protein clearance pathways","volume":"108","author":"Chou","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1892","DOI":"10.1021\/acs.jmedchem.9b01318","article-title":"P97: An emerging target for cancer, neurodegenerative diseases, and viral infections","volume":"63","author":"Huryn","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"101513","DOI":"10.1016\/j.tice.2021.101513","article-title":"Ubiquitin proteasome system and autophagy associated proteins in human testicular tumors","volume":"71","author":"Nakkas","year":"2021","journal-title":"Tissue Cell"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1016\/j.molonc.2016.09.005","article-title":"VCP inhibitors induce endoplasmic reticulum stress, cause cell cycle arrest, trigger caspase-mediated cell death and synergistically kill ovarian cancer cells in combination with Salubrinal","volume":"10","author":"Bastola","year":"2016","journal-title":"Mol. Oncol."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/6\/1079\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:48:23Z","timestamp":1760125703000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/6\/1079"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,3]]},"references-count":48,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["medicina59061079"],"URL":"https:\/\/doi.org\/10.3390\/medicina59061079","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,3]]}}}