Protein degradation by the ubiquitin-proteasome system is central to cell homeostasis and survival. Defects in this process are associated with diseases such as cancer and neurodegenerative disorders. The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The two end rings are each formed by seven a subunits, and the two central rings are each formed by seven subunits. Replacement of LMPY by LMP2/i increases the capacity of the immunoproteasome to cleave model peptides after hydrophobic and basic residues. LMP2/i mediates the cell survival pathway. Embryo implantation involves the invasion of placental extravillous trophoblast cells (EVTs) into the uterus. Normal human placentas or placentas from hydatidiform mole patients were collected and the expression of LMP2/i in different cell types including trophoblastic column (TC), cytotrophoblast cells (CTB) and syncytiotrophoblasts (STBs) was examined under different pathological states by pathological analysis. LMP2/i expression in TC of partial hydatidiform mole and complete hydatidiform mole placentas was higher than that in TC of normal human placentas. The overexpression of LMP2/i in trophoblast cells of hydatidiform moles may contribute to its highly invasive phenotype. LMP2/i-deficient mice reportedly exhibit uterine neoplasms, with a disease prevalence of 36% by 12 months of age. Further experiments with human and mouse uterine tissues clarified the biological significance of LMP2/i in malignant myometrium transformation and the cell cycle, which implicated LMP2/i as an anti-tumorigenic candidate. In this mini review, we covered recent insights into the molecular and cellular pathways involved in LMP2/i-mediated biological functions, with a particular focus on embryo implantation and uterine mesenchymal tumorigenesis.
| Published in | Journal of Gynecology and Obstetrics (Volume 1, Issue 1) |
| DOI | 10.11648/j.jgo.20130101.11 |
| Page(s) | 1-6 |
| Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
| Copyright |
Copyright © The Author(s), 2013. Published by Science Publishing Group |
LMP2/b1i, Implantation, Trophoblast, Leiomyosarcoma, Leiomyoma
| [1] | Coux O, Tanaka K, Goldberg AL. (1996) Structure and functions of the 20S and 26S proteasomes. Annu Rev Biochem 65:801–847. |
| [2] | Voges D, Zwickl P, Baumeister W. (1999) The 26S proteasome: a molecular machine designed for controlled proteolysis. Annu Rev Biochem 1999; 68:1015–1068. |
| [3] | Ciechanover A. (1998) The ubiquitin-proteasome pathway: on protein death and cell life. EMBO J 17: 7151–7160. |
| [4] | Craiu A, Gaczynska M, Akopian T, Gramm CF, Fenteany G, Goldberg AL, Rock KL. (1997) Lactacystin and clasto-lactacystin b-lactone modify multiple proteasome subunits and inhibit intracellular protein degradation and major histocompatibility complex class I antigen presentation. J Biol Chem 272: 13437–13445. |
| [5] | Rivett AJ, Bose S, Brooks P, Broadfoot KI. (2001) Regulation of proteasome complexes by interferon-g and phosphorylation. Biochemie 2001; 83: 363–366. |
| [6] | Lowe J, Stock D, Jap B, Zwickl P, Baumeister W, Huber R. (1995) Crystal structure of the 20S proteasome from the archacon T. acidophilum at 3.4 A° resolution. Science 268:533–539. |
| [7] | Groll M, Ditzel L, Lowe J, Stock D, Bochtler M, Bartunik HD, Huber R. (1997) Structure of 20S proteasome from yeast at 2.4 A° resolution. Nature 386:463–471. |
| [8] | Baumeister W, Walz J, Zuhl F, Seemuller E. (1998) The proteasome: paradigm of a self- compartmentalizing protease. Cell 92:367–380. |
| [9] | Schmidtke G, Kraft R, Kostka S, Henklein P, Frommel C, Lowe J, Huber R, Kloetzel PM, Schmidt M. (1996) Analysis of mammalian 20S proteasome biogenesis: the maturation of b subunits is an ordered two-step mechanism involving autocatalysis. EMBO J 15:6887–6898. |
| [10] | Kuchelkorn U, Frentzel S, Kraft R, Kostka S, Groettrup M, Kloetzel PM. Incorporation of major histocompatibility complex-encoded subunits LMP2 and LMP7 changes the quality of the 20S proteasome polypeptide processing products independent of interferon-g. Eur J Immunol 25:2605–2611. |
| [11] | Glynne R, Powis SH, Beck S, Kelly A, Kerr LA, Trowsdale J. (1991) A proteasome-related gene between the two ABC transporter loci in the class II region of the human MHC. Nature 353:357–360. |
| [12] | Fehling HJ, Swat W, Laplace C, Kuhn R, Rajewsky K, Muller U, von Boehmer H. (1994) MHC class I expression in mice lacking proteasome subunit LMP-7. Science 265:1234–1237. |
| [13] | Rock KL, Gramm C, Rothstein L, Clark K, Stein R, Dick L, Hwang D, and Goldberg A. (1994) Inhibition of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules. Cell 78:761–771. |
| [14] | Gaczynska M, Goldberg AL, Tanaka K, Hendil KB, Rock KL. (1996) Proteasome subunits X and Y alter peptidase activities in opposite ways to the interferon-g-induced subunits LMP2 and LMP7. J Biol Chem 271:17275–17280. |
| [15] | Ustrell V, Pratt G, Rechsteiner M. (1995) Effects of interferon-g and major histocompatibility complex encoded subunits on peptidase activities of human multicatalytic proteases. Proc Natl Acad Sci U S A 92: 584–588. |
| [16] | Reits EA, Benham AM, Plougaste B, Neefjes J, Trowsdale J. (1997) Dynamics of proteasome distribution in living cells. EMBO J 16:6087–6094. |
| [17] | Brooks P, Murray RZ, Mason GGF, Hendil KB, Rivett AJ. (2000) Association of immunoproteasome with the endoplasmic reticulum. Biochem J 352:611–615. |
| [18] | Finn CA. (1996) Implantation, menstruation and inflammation. Biol Rev Camb Philos Soc 61:313–328. |
| [19] | Waterhouse P, Denhardt DT, Khokha R. (1993) Temporal expression of tissue inhibitors of metalloproteinases in mouse reproductive tissues during gestation. Mol Reprod Dev 35:219–226. |
| [20] | Blankenship TN, King BF. (1994) Identification of 72-kilodalton type IV collagenase at sites of trophoblastic invasion of macaque spiral arteries. Placenta 15:177–187. |
| [21] | Hurskainen T, Hoyhtya M, Tuuttila A, Oikarinen A, Autio-Harmainen H. (1996) mRNA expressions of TIMP-1, -2, and -3 and 92-KD type I vcollagenase in early human placenta and decidual membrane as studie by in situ hybridization. J Histochem Cytochem 44:1379–1388. |
| [22] | Bebington C, Bell SC, Doherty FJ, Fazleabas AT, Fleming SD. (1999) Localization of ubiquitin and ubiquitin cross-reactive protein in human and baboon endometrium and decidua during the menstrual cycle and early pregnancy. Biol Reprod 60:920–928. |
| [23] | Bebington C, Doherty FJ, Fleming SD. (2000) Ubiquitin and ubiquitin-protein conjugates are present in human cytotrophoblast throughout gestation. Early Pregnancy 4:240–252. |
| [24] | Johnson GA, Austin KJ, Van Kirk EA, Hansen TR. (1998) Pregnancy and interferon-tau induce conjugation of bovine ubiquitin cross-reactive protein to cytosolic uterine proteins. Biol Reprod 58: 898–904. |
| [25] | Johnson GA, Spencer TE, Hansen TR, Austin KJ, Burghardt RC, Bazer FW. (1999) Expression of the interferon tau inducible ubiquitin crossreactive protein in the ovine uterus. Biol Reprod 61:312–318. |
| [26] | Austin KJ, Bany BM, Belden EL, Rempel LA, Cross JC, Hansen TR. (2003) Interferon-stimulated gene-15 (Isg15) expression is up-regulated in the mouse uterus in response to the implanting conceptus. Endocrinology 144:3107–3113. |
| [27] | Hayashi T, Kodama S, Faustman DL. (2000) LMP2 expression and proteasome activity in NOD mice. Nature Med. 6:1065-6. |
| [28] | Higashitsuji H, Liu Y, Mayer RJ, Fujita J. (2005) The oncoprotein gankyrin negatively regulates both p53 and RB by enhancing proteasomal degradation. Cell Cycle 4: 1335–1337. |
| [29] | Wang J, Maldonado MA. (2006) The Ubiquitin-Proteasome System and Its Role in Inflammatory and Autoimmune Diseases. Cell Mol Immunol 3: 255–261. |
| [30] | Muchamuel, T, Basler M, Aujay MA, Suzuki E, Kalim KW, Lauer C, Sylvain C, Ring ER, Shields J, Jiang J, Shwonek P, Parlati F, Demo SD, Bennett MK, Kirk CJ, Groettrup M. (2009) A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis. Nature Med 15: 781-788. |
| [31] | Van Kaer L, Ashton-Rickardt PG, Eichelberger M, Gaczynska M, Nagashima K, Rock KL, Goldberg AL, Doherty PC, Tonegawa S. (1994) Altered peptidase and viral-specifi c T cell response in LMP2 mutant mice. Immunity 1: 533-541. |
| [32] | Hayashi T, Faustman DL. (2002) Development of spontaneous uterine tumors in low molecular mass polypeptide-2 knockout mice. Cancer Res 62: 24-27. |
| [33] | http://www.informatics.jax.org/javawi2/servlet/WIFetch?page=alleleDetail&id=MGI:2152729#refs |
| [34] | Hayashi T, Horiuchi A, Sano K, Hiraoka N, Kanai Y, Shiozawa T, Tonegawa S, Konishi I. (2011) Molecular approach on uterine leiomyosarcoma: LMP2-deficient mice as an animal model of spontaneous uterine leiomyosarcoma. Sarcoma. 476498. Epub 2011 Mar 8. |
| [35] | Stohwasser R, Kuckelkorn U, Kraft R, Kostka S, Kloetzel PM. (1996) 20 S proteasome from LMP7 knock out mice reveals altered proteolytic activities and cleavage site preferences. FEBS Letters 383: 109-113. |
| [36] | Hayashi T, Kobayashi Y, Kohsaka S, Sano K. (2006) The mutation in the ATP-binding region of JAK1, identified in human uterine leiomyosarcomas, results in defective interferon-gamma inducibility of TAP1 and LMP2. Oncogene 25: 4016-4026. |
| [37] | Hayashi T, Horiuchi A, Sano K, Hiraoka N, Kasai M, Ichimura T, Nagase S, Ishiko O, Kanai Y, Yaegashi N, Aburatani H, Shiozawa T, Konishi I. (2011) Potential role of LMP2 as tumor-suppressor defines new targets for uterine leiomyosarcoma therapy. Sci Rep 1: 180|DOI:10.1038/ srep00180 |
| [38] | Hayashi T, Horiuchi A, Sano K, Hiraoka N, Kasai M, Ichimura T, Nagase S, Ishiko O, Kanai Y, Yaegashi N, Aburatani H, Shiozawa T, Konishi I. (2012) Potential role of LMP2 as an anti-oncogenic factor in human uterine leiomyosarcoma: morphological significance of calponin h1. FEBS Letter 586: 1824-31. |
| [39] | Hayashi T, Horiuchi A, Sano K, Hiraoka N, Ichimura T, Sudo T, Ishiko O, Yaegashi N, Aburatani H, Konishi I. Potential diagnostic biomarkers for human uterine mesenchymal tumors: Especially LMP2/1i and Cyclin B1-differential expression. Oncology Letter 2013. in-press |
| [40] | Kurma RJ. (2001) Pathology of the Female Genital Tract, 4th ed. New York, Springer-Verlag 2001; 4: 499. |
| [41] | Diagnostic Criteria for LMS, Adapted from 2003 WHO Guidelines: World Health Organization Classification of Tumours: Pathology and Genetics, Pathology and Genetics of Tumours of the Breast and Female Genital Organs. 2003; IARC Press, France. |
APA Style
Takuma Hayashi, Takuma Hayashi, Takuma Hayashi, Akiko Horiuchi, Kenji Sano, et al. (2013). The Proteasome Subunit LMP2/b1i In the Female Genital System. Journal of Gynecology and Obstetrics, 1(1), 1-6. https://doi.org/10.11648/j.jgo.20130101.11
ACS Style
Takuma Hayashi; Takuma Hayashi; Takuma Hayashi; Akiko Horiuchi; Kenji Sano, et al. The Proteasome Subunit LMP2/b1i In the Female Genital System. J. Gynecol. Obstet. 2013, 1(1), 1-6. doi: 10.11648/j.jgo.20130101.11
AMA Style
Takuma Hayashi, Takuma Hayashi, Takuma Hayashi, Akiko Horiuchi, Kenji Sano, et al. The Proteasome Subunit LMP2/b1i In the Female Genital System. J Gynecol Obstet. 2013;1(1):1-6. doi: 10.11648/j.jgo.20130101.11
Share This Article
Twitter
Linked In
Facebook
Copy
Download@article{10.11648/j.jgo.20130101.11,
author = {Takuma Hayashi and Takuma Hayashi and Takuma Hayashi and Akiko Horiuchi and Kenji Sano and Gal Gur and Gal Gur and Hiroyuki Aburatani and Tomoyuki Ichimura and Nobuo Yaegashi and Yae Kanai and Dorit Zharhary and Dorit Zharhary and Susumu Tonegawa and Ikuo Konishi},
title = {The Proteasome Subunit LMP2/b1i In the Female Genital System},
journal = {Journal of Gynecology and Obstetrics},
volume = {1},
number = {1},
pages = {1-6},
doi = {10.11648/j.jgo.20130101.11},
url = {https://doi.org/10.11648/j.jgo.20130101.11},
eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.jgo.20130101.11},
abstract = {Protein degradation by the ubiquitin-proteasome system is central to cell homeostasis and survival. Defects in this process are associated with diseases such as cancer and neurodegenerative disorders. The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The two end rings are each formed by seven a subunits, and the two central rings are each formed by seven subunits. Replacement of LMPY by LMP2/i increases the capacity of the immunoproteasome to cleave model peptides after hydrophobic and basic residues. LMP2/i mediates the cell survival pathway. Embryo implantation involves the invasion of placental extravillous trophoblast cells (EVTs) into the uterus. Normal human placentas or placentas from hydatidiform mole patients were collected and the expression of LMP2/i in different cell types including trophoblastic column (TC), cytotrophoblast cells (CTB) and syncytiotrophoblasts (STBs) was examined under different pathological states by pathological analysis. LMP2/i expression in TC of partial hydatidiform mole and complete hydatidiform mole placentas was higher than that in TC of normal human placentas. The overexpression of LMP2/i in trophoblast cells of hydatidiform moles may contribute to its highly invasive phenotype. LMP2/i-deficient mice reportedly exhibit uterine neoplasms, with a disease prevalence of 36% by 12 months of age. Further experiments with human and mouse uterine tissues clarified the biological significance of LMP2/i in malignant myometrium transformation and the cell cycle, which implicated LMP2/i as an anti-tumorigenic candidate. In this mini review, we covered recent insights into the molecular and cellular pathways involved in LMP2/i-mediated biological functions, with a particular focus on embryo implantation and uterine mesenchymal tumorigenesis.},
year = {2013}
}
TY - JOUR T1 - The Proteasome Subunit LMP2/b1i In the Female Genital System AU - Takuma Hayashi AU - Takuma Hayashi AU - Takuma Hayashi AU - Akiko Horiuchi AU - Kenji Sano AU - Gal Gur AU - Gal Gur AU - Hiroyuki Aburatani AU - Tomoyuki Ichimura AU - Nobuo Yaegashi AU - Yae Kanai AU - Dorit Zharhary AU - Dorit Zharhary AU - Susumu Tonegawa AU - Ikuo Konishi Y1 - 2013/06/30 PY - 2013 N1 - https://doi.org/10.11648/j.jgo.20130101.11 DO - 10.11648/j.jgo.20130101.11 T2 - Journal of Gynecology and Obstetrics JF - Journal of Gynecology and Obstetrics JO - Journal of Gynecology and Obstetrics SP - 1 EP - 6 PB - Science Publishing Group SN - 2376-7820 UR - https://doi.org/10.11648/j.jgo.20130101.11 AB - Protein degradation by the ubiquitin-proteasome system is central to cell homeostasis and survival. Defects in this process are associated with diseases such as cancer and neurodegenerative disorders. The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The two end rings are each formed by seven a subunits, and the two central rings are each formed by seven subunits. Replacement of LMPY by LMP2/i increases the capacity of the immunoproteasome to cleave model peptides after hydrophobic and basic residues. LMP2/i mediates the cell survival pathway. Embryo implantation involves the invasion of placental extravillous trophoblast cells (EVTs) into the uterus. Normal human placentas or placentas from hydatidiform mole patients were collected and the expression of LMP2/i in different cell types including trophoblastic column (TC), cytotrophoblast cells (CTB) and syncytiotrophoblasts (STBs) was examined under different pathological states by pathological analysis. LMP2/i expression in TC of partial hydatidiform mole and complete hydatidiform mole placentas was higher than that in TC of normal human placentas. The overexpression of LMP2/i in trophoblast cells of hydatidiform moles may contribute to its highly invasive phenotype. LMP2/i-deficient mice reportedly exhibit uterine neoplasms, with a disease prevalence of 36% by 12 months of age. Further experiments with human and mouse uterine tissues clarified the biological significance of LMP2/i in malignant myometrium transformation and the cell cycle, which implicated LMP2/i as an anti-tumorigenic candidate. In this mini review, we covered recent insights into the molecular and cellular pathways involved in LMP2/i-mediated biological functions, with a particular focus on embryo implantation and uterine mesenchymal tumorigenesis. VL - 1 IS - 1 ER -
Information
Email: