A Novel Transcriptional Repressor, Rhit, is Involved in Heat-inducible and Age-dependent Expression of Mpv17-like Protein, a Participant in Reactive Oxygen Species Metabolism

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2010 Mar 17

PMID 20231359

Citations 4

Authors

Reiko Iida

Misuzu Ueki

Toshihiro Yasuda

Affiliations

Soon will be listed here.

Abstract

Mpv17-like protein (M-LP) is a protein that has been suggested to be involved in the metabolism of reactive oxygen species. The two M-LP isoforms in mouse, M-LP(S) and M-LP(L), are generated by the alternative usage of promoters. M-LP(S) is expressed exclusively in kidneys after the age of 6 weeks, whereas M-LP(L) is expressed ubiquitously. To elucidate the molecular basis of M-LP(S) expression, we searched for cis-regulatory elements in the promoter region of M-LP(S) and identified heat shock element half-sites as positive elements and a Tramtrack 69K (Ttk 69K) binding site as a negative element. Furthermore, we isolated a novel transcription repressor, Rhit (regulator of heat-induced transcription), that binds to the Ttk 69K binding site within the M-LP(S) promoter by DNA affinity chromatography and confirmed its participation in the transcriptional regulation of M-LP(S) by RNA interference (RNAi). Sequence analysis revealed that Rhit contains a KRAB (Krüppel-associated box) domain and a DNA-binding domain composed of eight C(2)H(2)-type zinc fingers. Interestingly, exposure to heat shock stress resulted in the upregulation of M-LP(S) expression concurrent with the downregulation of Rhit expression. Moreover, the age-dependent expression of M-LP(S) was inversely correlated with that of Rhit. These observations strongly suggest that Rhit acts as a repressor in the heat-induced and age-dependent transcriptional regulation of M-LP(S).

Citing Articles

Transcriptomic and Functional Analyses of Two Cadmium Hyper-Enriched Duckweed Strains Reveal Putative Cadmium Tolerance Mechanisms.

Yang G, Huang L, Yang X, Li Z, Liao H, Mao K Int J Mol Sci. 2023; 24(15).

PMID: 37569533 PMC: 10418380. DOI: 10.3390/ijms241512157.

Knockout of Mpv17-Like Protein (M-LPH) Gene in Human Hepatoma Cells Results in Impairment of mtDNA Integrity through Reduction of TFAM, OGG1, and LIG3 at the Protein Levels.

Iida R, Ueki M, Yasuda T Oxid Med Cell Longev. 2018; 2018:6956414.

PMID: 30310528 PMC: 6166373. DOI: 10.1155/2018/6956414.

A universal mammalian vaccine cell line substrate.

Murray J, Todd K, Bakre A, Orr-Burks N, Jones L, Wu W PLoS One. 2017; 12(11):e0188333.

PMID: 29176782 PMC: 5703543. DOI: 10.1371/journal.pone.0188333.

Three Nonsynonymous Single Nucleotide Polymorphisms in the RhitH Gene Cause Reduction of the Repression Activity That Leads to Upregulation of M-LPH, a Participant in Mitochondrial Function.

Iida R, Ueki M, Fujihara J, Takeshita H, Kimura-Kataoka K, Yasuda T Biores Open Access. 2014; 2(6):440-7.

PMID: 24380054 PMC: 3869441. DOI: 10.1089/biores.2013.0042.

References

Zwacka R, Reuter A, Pfaff E, Moll J, Gorgas K, Karasawa M . The glomerulosclerosis gene Mpv17 encodes a peroxisomal protein producing reactive oxygen species. EMBO J. 1994; 13(21):5129-34. PMC: 395460. DOI: 10.1002/j.1460-2075.1994.tb06842.x. View

Kroeger P, Sarge K, Morimoto R . Mouse heat shock transcription factors 1 and 2 prefer a trimeric binding site but interact differently with the HSP70 heat shock element. Mol Cell Biol. 1993; 13(6):3370-83. PMC: 359798. DOI: 10.1128/mcb.13.6.3370-3383.1993. View

Laemmli U . Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970; 227(5259):680-5. DOI: 10.1038/227680a0. View

Heydari A, You S, Takahashi R, Sarge K, Richardson A . Age-related alterations in the activation of heat shock transcription factor 1 in rat hepatocytes. Exp Cell Res. 2000; 256(1):83-93. DOI: 10.1006/excr.2000.4808. View

Bellefroid E, Poncelet D, Lecocq P, Revelant O, Martial J . The evolutionarily conserved Krüppel-associated box domain defines a subfamily of eukaryotic multifingered proteins. Proc Natl Acad Sci U S A. 1991; 88(9):3608-12. PMC: 51501. DOI: 10.1073/pnas.88.9.3608. View

Vissing H, Meyer W, Aagaard L, Tommerup N, Thiesen H . Repression of transcriptional activity by heterologous KRAB domains present in zinc finger proteins. FEBS Lett. 1995; 369(2-3):153-7. DOI: 10.1016/0014-5793(95)00728-r. View

Iida R, Yasuda T, Tsubota E, Matsuki T, Kishi K . Cloning, mapping, genomic organization, and expression of mouse M-LP, a new member of the peroxisomal membrane protein Mpv17 domain family. Biochem Biophys Res Commun. 2001; 283(2):292-6. DOI: 10.1006/bbrc.2001.4769. View

Shamovsky I, Gershon D . Novel regulatory factors of HSF-1 activation: facts and perspectives regarding their involvement in the age-associated attenuation of the heat shock response. Mech Ageing Dev. 2004; 125(10-11):767-75. DOI: 10.1016/j.mad.2004.07.006. View

Fairall L, Harrison S, Travers A, Rhodes D . Sequence-specific DNA binding by a two zinc-finger peptide from the Drosophila melanogaster Tramtrack protein. J Mol Biol. 1992; 226(2):349-66. DOI: 10.1016/0022-2836(92)90952-g. View

10.

Iida R, Yasuda T, Tsubota E, Takatsuka H, Matsuki T, Kishi K . Human Mpv17-like protein is localized in peroxisomes and regulates expression of antioxidant enzymes. Biochem Biophys Res Commun. 2006; 344(3):948-54. DOI: 10.1016/j.bbrc.2006.04.008. View

11.

Iida R, Yasuda T, Aoyama M, Tsubota E, Matsuki T, Kishi K . Age-related changes of gene expression in mouse kidney: fluorescence differential display--PCR analyses. Mech Ageing Dev. 2000; 113(2):135-44. DOI: 10.1016/s0047-6374(99)00104-9. View

12.

Ahn S, Thiele D . Redox regulation of mammalian heat shock factor 1 is essential for Hsp gene activation and protection from stress. Genes Dev. 2003; 17(4):516-28. PMC: 195992. DOI: 10.1101/gad.1044503. View

13.

Iida R, Yasuda T, Tsubota E, Takatsuka H, Masuyama M, Matsuki T . A novel alternative spliced Mpv17-like protein isoform localizes in cytosol and is expressed in a kidney- and adult-specific manner. Exp Cell Res. 2004; 302(1):22-30. DOI: 10.1016/j.yexcr.2004.08.027. View

14.

Wagner G, Stettmaier K, Bors W, Sies H, Wagner E, Reuter A . Enhanced gamma-glutamyl transpeptidase expression and superoxide production in Mpv17-/- glomerulosclerosis mice. Biol Chem. 2001; 382(7):1019-25. DOI: 10.1515/BC.2001.128. View

15.

Spinazzola A, Viscomi C, Fernandez-Vizarra E, Carrara F, dAdamo P, Calvo S . MPV17 encodes an inner mitochondrial membrane protein and is mutated in infantile hepatic mitochondrial DNA depletion. Nat Genet. 2006; 38(5):570-5. DOI: 10.1038/ng1765. View

16.

Pavletich N, Pabo C . Zinc finger-DNA recognition: crystal structure of a Zif268-DNA complex at 2.1 A. Science. 1991; 252(5007):809-17. DOI: 10.1126/science.2028256. View

17.

Binder C, Weiher H, Exner M, Kerjaschki D . Glomerular overproduction of oxygen radicals in Mpv17 gene-inactivated mice causes podocyte foot process flattening and proteinuria: A model of steroid-resistant nephrosis sensitive to radical scavenger therapy. Am J Pathol. 1999; 154(4):1067-75. PMC: 1866567. DOI: 10.1016/S0002-9440(10)65359-X. View

18.

Gadgil H, Jarrett H . Oligonucleotide trapping method for purification of transcription factors. J Chromatogr A. 2002; 966(1-2):99-110. DOI: 10.1016/s0021-9673(02)00738-0. View

19.

Hunt C, Calderwood S . Characterization and sequence of a mouse hsp70 gene and its expression in mouse cell lines. Gene. 1990; 87(2):199-204. DOI: 10.1016/0378-1119(90)90302-8. View

20.

Abravaya K, Phillips B, Morimoto R . Attenuation of the heat shock response in HeLa cells is mediated by the release of bound heat shock transcription factor and is modulated by changes in growth and in heat shock temperatures. Genes Dev. 1991; 5(11):2117-27. DOI: 10.1101/gad.5.11.2117. View