Hostname: page-component-848d4c4894-cjp7w Total loading time: 0 Render date: 2024-06-22T10:23:54.290Z Has data issue: false hasContentIssue false
  • English
  • Français

Prothymosin alpha expression in the vertebrate testis: a comparative review

Published online by Cambridge University Press:  27 November 2017

Massimo Venditti  and
Sergio Minucci
Massimo Venditti
Affiliation:
Dipartimento di Medicina Sperimentale, Sez. Fisiologia Umana e Funzioni Biologiche Integrate, Università degli Studi della Campania ‘Luigi Vanvitelli’ 80138, Napoli, Italy.
Sergio Minucci*
Affiliation:
Dipartimento di Medicina Sperimentale, Università degli Studi della Campania ‘Luigi Vanvitelli’ 80138, Napoli, Italy.
*
All correspondence to: Sergio Minucci. Dipartimento di Medicina Sperimentale, Università degli Studi della Campania ‘Luigi Vanvitelli’ 80138, Napoli, Italy. Tel: +39 0815665829. E-mail: sergio.minucci@unicampania.it
Get access Rights & Permissions [Opens in a new window]

Summary

Prothymosin alpha (PTMA) is a highly acidic, intrinsically disordered protein that was first extracted from rat thymus and characterized as an immunogenic factor but soon detected in a variety of mammalian tissues. The presence of a nuclear localization signal and the adoption of a peculiar random-coil conformation are among the reasons behind its interaction with several molecular partners, hence at this time PTMA is known to be a very conserved and widely expressed molecule, involved in numerous and diverse biological processes. Only few studies have tried to weigh its possible involvement in reproduction, specifically in male gametogenesis: first reports have suggested that PTMA might be associated with the proliferative and early-meiotic phases of mammal spermatogenesis. Some years later, a comparative project on vertebrate spermatogenesis reported the isolation, for the first time, of prothymosin in a non-mammalian species, the amphibian Pelophylax esculentus. PTMA transcript and protein are localized in the germinal compartment, from spermatocytes to spermatozoa. A congruent pattern has been highlighted in studies on the fish Torpedo marmorata and Danio rerio, and in the mammal Rattus norvegicus, in which the expression of PTMA has been found in meiotic and post-meiotic germ cells inside testicular cysts and tubules. Moreover, its presence has been confirmed in rat and human spermatozoa (associated with the acrosome); its retention in the apical region of the head after the acrosome reaction revealed a striking conservation of the pattern during phylogenesis and suggested a possible role for the protein in gametogenesis and in fertilization.

Keywords

prothymosin alphaspermatogenesisVertebratesspermatozoatestis
Type
Review Article
Information
Zygote , Volume 25 , Issue 6 , December 2017 , pp. 760 - 770
Copyright
Copyright © Cambridge University Press 2017 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Adams, M.D., Kerlavage, A.R., Fleischmann, R.D., Fuldner, R.A., Bult, C.J., Lee, N.H., Kirkness, E.F., Weinstock, K.G., Gocayne, J.D., White, O., et al. (1995). Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence. Nature 377 (6547 Suppl.), 3–174.Google Scholar
Aniello, F., De, Branno, M., Rienzo, G., Ferrara, D., Palmiero, C. & Minucci, S. (2002). First evidence of prothymosin alpha in a non-mammalian vertebrate and its involvement in the spermatogenesis of the frog Rana esculenta . Mech. Dev. 110, 213–7.Google Scholar
Baxevanis, C.N., Thanos, D., Reclos, G.J., Anastasopoulos, E., Tsokos, G.C., Papamatheakis, J. & Papamichail, M. (1992). Prothymosin alpha enhances human and murine MHC class II surface antigen expression and messenger RNA accumulation. J. Immunol. 148, 1979–84.CrossRefGoogle ScholarPubMed
Billard, R. (1990). Spermatogenesis in teleost, fish. In Lamming, G.E. (ed.), Marshall's Physiology of Reproduction. Reproduction in Males vol. 2, pp. 183–212. Churchill Livingstone, Edinburgh.Google Scholar
Cho, C., Willis, W.D., Goulding, E.H., Jung-Ha, H., Choi, Y.C., Hecht, N.B. & Eddy, E.M. (2001). Haploinsufficiency of protamine-1 or -2 causes infertility in mice. Nat. Genet. 28, 82–6.Google Scholar
Clinton, M., Frangou-Lazaridis, M., Panneerselvam, C. & Horecker, B.L. (1989). Prothymosin alpha and parathymosin: mRNA and polypeptide levels in rodent tissues. Arch. Biochem. Biophys. 269, 256–63.CrossRefGoogle ScholarPubMed
Doenecke, D., Drabent, B., Bode, C., Bramlage, B., Franke, K., Gavenis, K., Kosciessa, U. & Witt, O. (1997). Histone gene expression and chromatin structure during spermatogenesis. Adv. Exp. Med. Biol. 424, 37–48.Google Scholar
Domínguez, F., Magdalena, C., Cancio, E., Rosón, E., Paredes, J., Loidi, L., Zalvide, J., Fraga, M., Forteza, J., Regueiro, B.J., et al. (1993). Tissue concentrations of prothymosin alpha: a novel proliferation index of primary breast cancer. Eur. J. Cancer 29A, 893–7.Google Scholar
Donizetti, A., Liccardo, D., Esposito, D., Del, Gaudio, R., Locascio, A., Ferrara, D., Minucci, S. & Aniello, F. (2008). Differential expression of duplicated genes for prothymosin alpha during zebrafish development. Dev. Dyn. 237, 1112–8.CrossRefGoogle ScholarPubMed
Dosil, M., Freire, M. & Gómez-Márquez, J. (1990). Tissue-specific and differential expression of prothymosin alpha gene during rat development. FEBS Lett. 269, 373–6.CrossRefGoogle ScholarPubMed
Enkemann, S.A., Wang, R.H., Trumbore, M.W. & Berger, S.L. (2000a). Functional discontinuities in prothymosin alpha caused by caspase cleavage in apoptotic cells. J. Cell. Physiol. 182, 256–68.Google Scholar
Enkemann, S.A., Ward, R.D. & Berger, S.L. (2000b). Mobility within the nucleus and neighboring cytosol is a key feature of prothymosin alpha. J. Histochem. Cytochem. 48, 1341–55.Google Scholar
Eschenfeldt, W.H., Manrow, R.E., Krug, M.S. & Berger, S.L. (1989). Isolation and partial sequencing of the human prothymosin alpha gene family. Evidence against export of the gene products. J. Biol. Chem. 264, 7546–55.Google Scholar
Evstafieva, A.G., Belov, G.A., Kalkum, M., Chichkova, N.V., Bogdanov, A.A., Agol, V.I. & Vartapetian, A.B. (2000). Prothymosin alpha fragmentation in apoptosis. FEBS Lett. 467, 150–4.Google Scholar
Ferrara, D., Izzo, G., Liguori, L., d'Istria, M., Aniello, F. & Minucci, S. (2009). Evidence for the involvement of prothymosin alpha in the spermatogenesis of the frog Rana esculenta . J. Exp. Zool. A Ecol. Genet. Physiol. 311, 1–10.Google Scholar
Ferrara, D., Izzo, G., Pariante, P., Donizetti, A., d'Istria, M., Aniello, F. & Minucci, S. (2010). Expression of prothymosin alpha in meiotic and post-meiotic germ cells during the first wave of rat spermatogenesis. J. Cell. Physiol. 224, 362–8.Google Scholar
Ferrara, D., Pariante, P., Di, Matteo, L., Serino, I., Oko, R. & Minucci, S. (2013). First evidence of prothymosin α localization in the acrosome of mammalian male gametes. J. Cell. Physiol. 228, 1629–37.CrossRefGoogle ScholarPubMed
Frangou-Lazaridis, M., Clinton, M., Goodall, G.J. & Horecker, B.L. (1988). Prothymosin alpha and parathymosin: amino acid sequences deduced from the cloned rat spleen cDNAs. Arch. Biochem. Biophys. 263, 305–10.Google Scholar
Gast, K., Damaschun, H., Eckert, K., Schulze-Forster, K., Maurer, H.R., Müller-Frohne, M., Zirwer, D., Czarnecki, J. & Damaschun, G. (1995). Prothymosin alpha: a biologically active protein with random coil conformation. Biochemistry 34, 13211–8.CrossRefGoogle ScholarPubMed
Gómez-Márquez, J. & Rodríguez, P. (1998). Prothymosin alpha is a chromatin-remodelling protein in mammalian cells. Biochem. J. 333, 1–3.Google Scholar
Gómez-Márquez, J. (2007). Function of prothymosin alpha in chromatin decondensation and expression of thymosin beta-4 linked to angiogenesis and synaptic plasticity. Ann. N. Y. Acad. Sci. 1112, 201–9.CrossRefGoogle Scholar
Grier, H.J. (1993). Comparative organization of Sertoli cells including the Sertoli cell barrier. In Russell, L.D. & Griswold, M.D. (eds) The Sertoli Cell, pp. 704–730. Cache River Press, Clearwater, Florida, USA.Google Scholar
Hannappel, E. & Huff, T. (2003). The thymosins. Prothymosin alpha parathymosin and beta-thymosins: structure and function. Vitam. Horm. 66, 257–96.Google Scholar
Haritos, A.A., Goodall, G.J. & Horecker, B.L. (1984a). Prothymosin alpha: isolation and properties of the major immunoreactive form of thymosin alpha 1 in rat thymus. Proc. Natl. Acad. Sci. USA 81, 1008–11.CrossRefGoogle ScholarPubMed
Haritos, A.A., Tsolas, O. & Horecker, B.L. (1984b). Distribution of prothymosin alpha in rat tissues. Proc. Natl. Acad. Sci. USA 81, 1391–3.Google Scholar
Huszno, J. & Klag, J. (2012). The reproductive cycle in the male gonads of Danio rerio (Teleostei, Cyprinidae). Stereological analysis. Micron 43, 666–72.Google Scholar
Iannou, K., Samara, P., Livaniou, E., Derhovanessian, E. & Tsitsilonis, O.E. (2012). Prothymosin alpha: a ubiquitous polypeptide with potential use in cancer diagnosis and therapy. Cancer Immunol. Immunother. 61, 599–614.CrossRefGoogle Scholar
Jiang, X., Kim, H.E., Shu, H., Zhao, Y., Zhang, H., Kofron, J., Donnelly, J., Burns, D., Ng, S.C., Rosenberg, S. & Wang, X. (2003). Distinctive roles of PHAP proteins and prothymosin alpha in a death regulatory pathway. Science 299, 223–6.Google Scholar
Karetsou, Z., Sandaltzopoulos, R., Frangou-Lazaridis, M., Lai, C.Y., Tsolas, O., Becker, P.B. & Papamarcaki, T. (1998). Prothymosin alpha modulates the interaction of histone H1 with chromatin. Nucleic Acids Res. 26, 3111–8.CrossRefGoogle ScholarPubMed
Karetsou, Z., Kretsovali, A., Murphy, C., Tsolas, O. & Papamarcaki, T. (2002). Prothymosin alpha interacts with the CREB-binding protein and potentiates transcription. EMBO Rep. 3, 361–6.Google Scholar
Karetsou, Z., Martic, G., Tavoulari, S., Christoforidis, S., Wilm, M., Gruss, C. & Papamarcaki, T. (2004). Prothymosin alpha associates with the oncoprotein SET and is involved in chromatin decondensation. FEBS Lett. 577, 496–500.CrossRefGoogle ScholarPubMed
Malicet, C., Giroux, V., Vasseur, S., Dagorn, J.C., Neira, J.L. & Iovanna, J.L. (2006). Regulation of apoptosis by the p8/prothymosin alpha complex. Proc. Natl Acad. Sci. USA 103, 2671–6.Google Scholar
Manandhar, G. & Toshimori, K. (2001). Exposure of sperm head equatorin after acrosome reaction and its fate after fertilization in mice. Biol. Reprod. 65, 1425–36.Google Scholar
Manrow, R.E., Leone, A., Krug, M.S., Eschenfeldt, W.H. & Berger, S.L. (1992). The human prothymosin alpha gene family contains several processed pseudogenes lacking deleterious lesions. Genomics 13, 319–31.Google Scholar
Martini, P.G., Delage-Mourroux, R., Kraichely, D.M. & Katzenellenbogen, B.S. (2000). Prothymosin alpha selectively enhances estrogen receptor transcriptional activity by interacting with a repressor of estrogen receptor activity. Mol. Cell. Biol. 20, 6224–32.Google Scholar
Martini, P.G. & Katzenellenbogen, B.S. (2003). Modulation of estrogen receptor activity by selective coregulators. J. Steroid. Biochem. Mol. Biol. 85, 117–22.Google Scholar
Miranda, P.V., Allaire, A., Sosnik, J. & Visconti, P.E. (2009). Localization of low-density detergent-resistant membrane proteins in intact and acrosome-reacted mouse sperm. Biol. Reprod. 80, 897–904.Google Scholar
Mosoian, A. (2011). Intracellular and extracellular cytokine-like functions of prothymosin α: implications for the development of immunotherapies. Future Med. Chem. 3, 1199–208.CrossRefGoogle ScholarPubMed
Oko, R. & Sutovsky, P. (2009). Biogenesis of sperm perinuclear theca and its role in sperm functional competence and fertilization. J. Reprod. Immunol. 83, 2–7.Google Scholar
Pan, L.X., Haritos, A.A., Wideman, J., Komiyama, T., Chang, M., Stein, S., Salvin, S.B. & Horecker, B.L. (1986). Human prothymosin alpha: amino acid sequence and immunologic properties. Arch. Biochem. Biophys. 250, 197–201.Google Scholar
Parenti, L.R. & Grier, H.J. (2004). Evolution and phylogeny of gonad morphology in bony fishes. Integr. Comp. Biol. 44, 333–48.Google Scholar
Pariante, P., Dotolo, R., Venditti, M., Ferrara, D., Donizetti, A., Aniello, F. & Minucci, S. (2016). Prothymosin alpha expression and localization during the spermatogenesis of Danio rerio . Zygote 24, 583–93.Google Scholar
Piñeiro, A., Cordero, O.J. & Nogueira, M. (2000). Fifteen years of prothymosin alpha: contradictory past and new horizons. Peptides 21, 1433–46.Google Scholar
Prisco, M., Liguoro, A., D'Onghia, B., Ricchiari, L., Andreuccetti, P. & Angelini, F. (2002). Fine structure of Leydig and Sertoli cells in the testis of immature and mature spotted ray Torpedo marmorata . Mol. Reprod. Dev. 63, 192–201.Google Scholar
Prisco, M., Liguoro, A., Comitato, R., Cardone, A., D'Onghia, B., Ricchiari, L., Angelini, F. & Andreuccetti, P. (2003). Apoptosis during spermatogenesis in the spotted ray Torpedo marmorata . Mol. Reprod. Dev. 64, 341–8.Google Scholar
Prisco, M., Liguoro, A., Ricchiari, L., Del, Giudice, G., Angelini, F. & Andreuccetti, P. (2008). Immunolocalization of 3β-HSD. and 17β-HSD. in the testis of the spotted ray Torpedo marmorata. Gen. Comp. Endocrinol. 155, 157–63.Google Scholar
Prisco, M., Donizetti, A., Aniello, F., Locascio, A., Del, Giudice, G., Agnese, M., Angelini, F. & Andreuccetti, P. (2009). Expression of prothymosin alpha during the spermatogenesis of the spotted ray Torpedo marmorata . Gen. Comp. Endocrinol. 164, 70–6.Google Scholar
Pudney, J. (1996). Comparative cytology of the Leydig cell. In Payne, A.M., Hardy, M.P. & Russell, L.D. (eds), The Leydig Cell, pp. 611–57. Vienna, Cache River.Google Scholar
Rastogi, R.K. & Iela, L. (1992). Spermatogenesis in amphibia: dynamics and regulation. In Dallai, R. (ed.), Sex, Origin and Evolution, pp. 231–49. Modena, Mucchi.Google Scholar
Rodríguez, P., Viñuela, J.E., Alvarez-Fernández, L., Buceta, M., Vidal, A., Domínguez, F. & Gómez-Márquez, J. (1998). Overexpression of prothymosin alpha accelerates proliferation and retards differentiation in HL-60 cells. Biochem. J. 331, 753–61.Google Scholar
Rosón, E., Gallego, R., García-Caballero, T., Heimer, E.P., Felix, A.M. & Domínguez, F. (1990). Prothymosin alpha expression is associated to cell division in rat testis. Histochemistry 94, 597–9.Google Scholar
Rubtsov, Iu.P. & Vartapetian, A.B. (1995). [New intronless members of human prothymosin alpha genes]. Mol. Biol. (Mosk) 29, 1320–5. [Article in Russian].Google Scholar
Samara, P., Karachaliou, C.E., Ioannou, K., Papaioannou, N.E., Voutsas, I.F., Zikos, C., Pirmettis, I., Papadopoulos, M., Kalbacher, H., Livaniou, E., Tsitsilonis, O.E. & Voelter, W. (2017). Prothymosin alpha: an alarmin and more. . . Curr. Med. Chem. 24, 1747–60.Google Scholar
Schulz, RW, de França, L.R., Lareyre, J.J., Le, Gac, F., Chiarini-Garcia, H., Nobrega, R.H. & Miura, T. (2010). Spermatogenesis in fish. Comp. Endocrinol. 165, 390–411.Google Scholar
Skopeliti, M., Voutsas, I.F., Klimentzou, P., Tsiatas, M.L., Beck, A., Bamias, A., Moraki, M., Livaniou, E., Neagu, M., Voelter, W. & Tsitsilonis, O.E. (2006). The immunologically active site of prothymosin alpha is located at the carboxy-terminus of the polypeptide. Evaluation of its in vitro effects in cancer patients. Cancer Immunol. Immunother. 55, 1247–57.CrossRefGoogle ScholarPubMed
Stanley, H.P. (1966). The structure and development of the seminiferous follicle in Scyliorhinus caniculus and Torpedo marmorata (Elasmobranchii). Z. Zellforsch. Mikrosk. Anat. 75, 453–68.Google Scholar
Szabo, P., Panneerselvam, C., Clinton, M., Frangou-Lazaridis, M., Weksler, D., Whittington, E., Macera, M.J., Grzeschik, K.H., Selvakumar, A. & Horecker, B.L. (1993). Prothymosin alpha gene in humans: organization of its promoter region and localization to chromosome 2. Hum. Genet. 90, 629–34.CrossRefGoogle ScholarPubMed
Toshimori, K. (2009). Dynamics of the mammalian sperm head: modifications and maturation events from spermatogenesis to egg activation. Adv. Anat. Embryol. Cell. Biol. 204, 5–94.Google Scholar
Trumbore, M.W., Manrow, R.E. & Berger, S.L. (1998). Prothymosin alpha is not found in yeast. Protein Expr. Purif. 13, 383–8.Google Scholar
Tsitsiloni, O.E., Stiakakis, J., Koutselinis, A., Gogas, J., Markopoulos, C., Yialouris, P., Bekris, S., Panoussopoulos, D., Kiortsis, V., Voelter, W., et al. (1993). Expression of alpha-thymosins in human tissues in normal and abnormal growth. Proc. Natl. Acad. Sci. USA 90, 9504–7.Google Scholar
Ueda, H. (2009). Prothymosin alpha and cell death mode switch a novel target for the prevention of cerebral ischemia-induced damage. Pharmacol. Ther. 123, 323–33.Google Scholar
Ueda, H., Matsunaga, H. & Halder, S.K. (2012). Prothymosin α plays multifunctional cell robustness roles in genomic epigenetic and nongenomic mechanisms. Ann. N. Y. Acad. Sci. 1269, 34–43.Google Scholar
Voutsas, I.F., Baxevanis, C.N., Gritzapis, A.D., Missitzis, I., Stathopoulos, G.P., Archodakis, G., Banis, C., Voelter, W. & Papamichail, M. (2000). Synergy between interleukin-2 and prothymosin alpha for the increased generation of cytotoxic T lymphocytes against autologous human carcinomas. Cancer Immunol. Immunother. 49, 449–58.Google Scholar
Wang, M. & Pan, J.Y. (2007). Prothymosin alpha and tumor: current status and perspective. Chin. J. Cancer 26, 333–6.Google Scholar
Wu, C.G., Habib, N.A., Mitry, R.R., Reitsma, P.H., van, Deventer, S.J. & Chamuleau, R.A. (1997). Overexpression of hepatic prothymosin alpha a novel marker for human hepatocellular carcinoma. Br. J. Cancer 76, 1199–204.Google Scholar
Yu, Y., Eriksson, P. & Stillman, D.J. (2000). Architectural transcription factors and the SAGA complex function in parallel pathways to activate transcription. Mol. Cell. Biol. 20, 2350–7.Google Scholar
Zhang, M., Cui, F., Lu, S., Lu, H., Jiang, T., Chen, J., Zhang, X., Jin, Y., Peng, Z. & Tang, H. (2014). Increased expression of prothymosin-α independently or combined with TP53 correlates with poor prognosis in colorectal cancer. Int. J. Clin. Exp. Pathol. 7, 4867–76.Google Scholar