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2007 | 54 | 1 |

Tytuł artykułu

The structural and functional analysis of the human HSPA2 gene promoter region

Warianty tytułu

Języki publikacji

EN

Abstrakty

EN
HSPA2 is a human counterpart of the testis-specific rodent Hst70/Hsp70.2 gene. In contrast to the latter, the expression of the human HSPA2 gene is not limited to the testis, and recent data show that human tumor cells can express this gene at significant levels. The characteristics of HSPA2 expression suggests that it can influence the phenotype and survival of cancer cells similarly as overexpression of major members of the HSP70 gene family. Until now, neither the structure of the transcription unit of the human HSPA2 gene has been established nor a functional analysis of its promoter performed. In this study we established that the human HSPA2 gene, in contrast to its rodent counterparts, is intronless and has a single transcription start site. We also show that the same type of HSPA2 transcripts are synthesized in the testes and in cancer cell lines. In order to perform a functional study of the HSPA2 promoter, we used a transient transfection assay and found that the 392 bp fragment upstream of the ATG codon was a minimal region required for efficient transcription, while a 150 bp deletion from the 5' end of this region dramatically reduced the promoter activity. Delineation of the minimal promoter is a basic step toward identifiying the cis and trans elements involved in the regulation of the HSPA2 gene expression in cancer cells.

Wydawca

-

Rocznik

Tom

54

Numer

1

Opis fizyczny

p.99-106,fig.,ref.

Twórcy

autor
  • Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeze Armii Krajowej 15, 44-101 Gliwice, Poland
autor
autor

Bibliografia

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  • Dix DJ, Allen JW, Collins BW, Mori C, Nakamura N, Poorman- Allen P, Goulding EH, Eddy EM (1996) Targeted gene disruption of Hsp70–2 results in failed meiosis, germ cell apoptosis, and male infertility. Proc Natl Acad Sci USA 93: 3264–8326.
  • Dix DJ, Allen JW, Collins BW, Poorman-Allen P, Mori C, Blizard DR, Brown PR, Goulding EH, Strong BD, Eddy EM (1997) HSP70-2 is required for desynapsis of synaptonemal complexes during meiotic prophase in juvenile and adult mouse spermatocytes. Development 124: 4595–4603.
  • Eddy EM (2002) Male germ cell gene expression. Recent Prog Horm Res 57: 103–128.
  • Huszar G, Stone K, Dix D, Vigue L (2000) Putative creatine kinase M-isoform in human sperm is identified as the 70–kilodalton heat shock protein HspA2. Biol Reprod 63: 925–932.
  • Huszar G, Ozkavukcu S, Jakab A, Celik-Ozenci C, Sati GL, Cayli S (2006) Hyaluronic acid binding ability of human sperm reflects cellular maturity and fertilizing potential: selection of sperm for intracytoplasmic sperm injection. Curr Opin Obstet Gynecol 18: 260–267.
  • Krawczyk Z, Mali P, Parvinen M (1988a) Expression of a testis-specific hsp70 gene-related RNA in defined stages of rat seminiferous epithelium. J Cell Biol 107: 1317– 1323
  • Krawczyk Z, Wisniewski J, Biesiada E (1988b) A rat testis- specific hsp70 gene-related transcript is coded by a novel gene from the hsp70 multigene family. Acta Biochim Polon 35: 377–385.
  • Krawczyk Z, Schmid W, Harkonen P, Wolniczek P (1993) The ERE-like sequence from the promoter region of the testis specific hsp70-related gene is not estrogen responsive. Cell Biol Int 17: 245–253.
  • Rohde M, Daugaard M, Jensen MH, Helin K, Nylandsted J, Jaattela M (2005) Members of the heat-shock protein 70 family promote cancer cell growth by distinct mechanisms. Genes Dev 19: 570–582.
  • Scanlan MJ, Simpson AJ, Old LJ (2004) The cancer/testis genes: review, standardization, and commentary. Cancer Immun 4: 1.
  • Ścieglińska D, Widłak W, Rusin M, Markkula M, Krawczyk Z (1997) Expression of the testis-specific HSP70-related gene (hst70 gene) in somatic non-testicular rat tissues revealed by RT-PCR and transgenic mice analysis. Cell Biol Int 21: 813–821.
  • Ścieglińska D, Widłak W, Konopka W, Poutanen M, Rahman N, Huhtaniemi I, Krawczyk Z (2001) Structure of the 5’ region part of the hst70 gene transcription unit: presence of an intron and multiple initiation sites. Biochem J 359: 129–137.
  • Ścieglińska D, Vydra N, Krawczyk Z, Widlak W (2004) Location of promoter elements necessary and sufficient to direct testis-specific expression of the Hst70/Hsp70.2 gene. Biochem J 379: 739–747.
  • Shin BK, Wang H, Yim AM, Le Naour F, Brichory F, Jang JH, Zhao R, Puravs E, Tra J, Michael CW, Misek DE, Hanash SM (2003) Global profiling of the cell surface proteome of cancer cells uncovers an abundance of proteins with chaperone function. J Biol Chem 278: 7607–7616.
  • Son WY, Hwang SH, Han CT, Lee JH, Kim S, Kim YC (1999) Specific expression of heat shock protein HspA2 in human male germ cells. Mol Hum Reprod 5: 1122– 1126.
  • Widlak W, Markkula M, Krawczyk Z, Huhtaniemi I (1994) Functional analysis of spermatocyte-specific hst70 gene promoter in transgenic mice. Acta Biochim Polon 41: 103–105.
  • Widłak W, Markkula M, Krawczyk Z, Kananen K, Huhtaniemi I (1995) A 252 bp upstream region of the rat spermatocyte-specific hst70 gene is sufficient to promote expression of the hst70–CAT hybrid gene in testis and brain of transgenic mice. Biochim Biophys Acta 1264: 191–200.
  • Widlak W, Scieglinska D, Vydra N, Malusecka E, Krawczyk Z (2003) In vivo electroporation of the testis versus transgenic mice model in functional studies of spermatocyte- specific hst70 gene promoter: A comparative study. Mol Reprod Dev 65: 382–388.
  • Yesilli C, Mungan G, Seckiner I, Akduman B, Acikgoz S, Altan K, Mungan A (2005) Effect of varicocelectomy on sperm creatine kinase, HspA2 chaperone protein (creatine kinase-M type), LDH, LDH-X, and lipid peroxidation product levels in infertile men with varicocele. Urology 66: 610–615.
  • Zakeri ZF, Wolgemuth DJ, Hunt CR (1988) Identification and sequence analysis of a new member of the mouse HSP70 gene family and characterization of its unique cellular and developmental pattern of expression in the male germ line. Mol Cell Biol 8: 2925–2932.
  • Zhu D, Dix DJ, Eddy EM (1997) HSP70–2 is required for CDC2 kinase activity in meiosis I of mouse spermatocytes. Development 124: 3007-3014

Typ dokumentu

Bibliografia

Identyfikatory

Identyfikator YADDA

bwmeta1.element.agro-article-03b04f0a-430a-4727-b32d-98e733142cee
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