NRF-1 is the major transcription factor regulating the expression of the human TOMM34 gene

José R. Blesa, Jesús A. Prieto-Ruiz, Beth A. Abraham, Bridget L. Harrison, Anita A. Hegde, José Hernández-Yago

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The human TOMM34 gene encodes a cytosolic protein with chaperone-like activity that helps import some preproteins to the mitochondria by keeping them in an unfolded, import-compatible state. TOMM34 was found to be upregulated frequently in colorectal tumors, suggesting that it also has a role in the growth of cancer cells. In this context, TOMM34 is a potential target for novel anticancer drugs, and it might also be used in the diagnosis of colorectal cancer. Nuclear respiratory factors (NRFs) play an important role in governing the nuclear-mitochondrial interactions implicated in mitochondrial biogenesis. Our previous studies revealed that NRFs promote the expression of the major members of the mitochondrial transport machinery, TOMM70 and TOMM20. Here we report the existence of binding sites for NRF-1, Sp1, and NRF-2 in the 5′ region of the human TOMM34 gene. We determined the effects of mutations at these sites on promoter activity in HeLa S3 and A204 cells, in conjunction with chromatin immunoprecipitation experiments, electrophoretic mobility shift assays, and in vivo methylation analysis of the promoter region. We conclude that NRF-1 is the main transcription factor regulating the expression of TOMM34. Sp1 interacts with NRF-1 to stimulate the promoter's full activity.

Original languageEnglish (US)
Pages (from-to)46-56
Number of pages11
JournalBiochemistry and Cell Biology
Volume86
Issue number1
DOIs
StatePublished - Feb 2008

Fingerprint

Nuclear Respiratory Factor 1
Nuclear Respiratory Factors
Transcription Factors
Genes
A 204
Colorectal Neoplasms
GA-Binding Protein Transcription Factor
Electrophoretic mobility
Mitochondria
Methylation
Chromatin Immunoprecipitation
Electrophoretic Mobility Shift Assay
Organelle Biogenesis
Genetic Promoter Regions
Chromatin
Machinery
Tumors
Assays
Binding Sites
Cells

Keywords

  • Mitochondrial import
  • NRF-1
  • Nuclear respiratory factor-1
  • Sp1
  • TOMM34

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Blesa, J. R., Prieto-Ruiz, J. A., Abraham, B. A., Harrison, B. L., Hegde, A. A., & Hernández-Yago, J. (2008). NRF-1 is the major transcription factor regulating the expression of the human TOMM34 gene. Biochemistry and Cell Biology, 86(1), 46-56. https://doi.org/10.1139/O07-151

NRF-1 is the major transcription factor regulating the expression of the human TOMM34 gene. / Blesa, José R.; Prieto-Ruiz, Jesús A.; Abraham, Beth A.; Harrison, Bridget L.; Hegde, Anita A.; Hernández-Yago, José.

In: Biochemistry and Cell Biology, Vol. 86, No. 1, 02.2008, p. 46-56.

Research output: Contribution to journalArticle

Blesa, JR, Prieto-Ruiz, JA, Abraham, BA, Harrison, BL, Hegde, AA & Hernández-Yago, J 2008, 'NRF-1 is the major transcription factor regulating the expression of the human TOMM34 gene', Biochemistry and Cell Biology, vol. 86, no. 1, pp. 46-56. https://doi.org/10.1139/O07-151
Blesa, José R. ; Prieto-Ruiz, Jesús A. ; Abraham, Beth A. ; Harrison, Bridget L. ; Hegde, Anita A. ; Hernández-Yago, José. / NRF-1 is the major transcription factor regulating the expression of the human TOMM34 gene. In: Biochemistry and Cell Biology. 2008 ; Vol. 86, No. 1. pp. 46-56.
@article{e0ffb73bdc444aea9a3d0bc72d7739db,
title = "NRF-1 is the major transcription factor regulating the expression of the human TOMM34 gene",
abstract = "The human TOMM34 gene encodes a cytosolic protein with chaperone-like activity that helps import some preproteins to the mitochondria by keeping them in an unfolded, import-compatible state. TOMM34 was found to be upregulated frequently in colorectal tumors, suggesting that it also has a role in the growth of cancer cells. In this context, TOMM34 is a potential target for novel anticancer drugs, and it might also be used in the diagnosis of colorectal cancer. Nuclear respiratory factors (NRFs) play an important role in governing the nuclear-mitochondrial interactions implicated in mitochondrial biogenesis. Our previous studies revealed that NRFs promote the expression of the major members of the mitochondrial transport machinery, TOMM70 and TOMM20. Here we report the existence of binding sites for NRF-1, Sp1, and NRF-2 in the 5′ region of the human TOMM34 gene. We determined the effects of mutations at these sites on promoter activity in HeLa S3 and A204 cells, in conjunction with chromatin immunoprecipitation experiments, electrophoretic mobility shift assays, and in vivo methylation analysis of the promoter region. We conclude that NRF-1 is the main transcription factor regulating the expression of TOMM34. Sp1 interacts with NRF-1 to stimulate the promoter's full activity.",
keywords = "Mitochondrial import, NRF-1, Nuclear respiratory factor-1, Sp1, TOMM34",
author = "Blesa, {Jos{\'e} R.} and Prieto-Ruiz, {Jes{\'u}s A.} and Abraham, {Beth A.} and Harrison, {Bridget L.} and Hegde, {Anita A.} and Jos{\'e} Hern{\'a}ndez-Yago",
year = "2008",
month = "2",
doi = "10.1139/O07-151",
language = "English (US)",
volume = "86",
pages = "46--56",
journal = "Biochemistry and Cell Biology",
issn = "0829-8211",
publisher = "National Research Council of Canada",
number = "1",

}

TY - JOUR

T1 - NRF-1 is the major transcription factor regulating the expression of the human TOMM34 gene

AU - Blesa, José R.

AU - Prieto-Ruiz, Jesús A.

AU - Abraham, Beth A.

AU - Harrison, Bridget L.

AU - Hegde, Anita A.

AU - Hernández-Yago, José

PY - 2008/2

Y1 - 2008/2

N2 - The human TOMM34 gene encodes a cytosolic protein with chaperone-like activity that helps import some preproteins to the mitochondria by keeping them in an unfolded, import-compatible state. TOMM34 was found to be upregulated frequently in colorectal tumors, suggesting that it also has a role in the growth of cancer cells. In this context, TOMM34 is a potential target for novel anticancer drugs, and it might also be used in the diagnosis of colorectal cancer. Nuclear respiratory factors (NRFs) play an important role in governing the nuclear-mitochondrial interactions implicated in mitochondrial biogenesis. Our previous studies revealed that NRFs promote the expression of the major members of the mitochondrial transport machinery, TOMM70 and TOMM20. Here we report the existence of binding sites for NRF-1, Sp1, and NRF-2 in the 5′ region of the human TOMM34 gene. We determined the effects of mutations at these sites on promoter activity in HeLa S3 and A204 cells, in conjunction with chromatin immunoprecipitation experiments, electrophoretic mobility shift assays, and in vivo methylation analysis of the promoter region. We conclude that NRF-1 is the main transcription factor regulating the expression of TOMM34. Sp1 interacts with NRF-1 to stimulate the promoter's full activity.

AB - The human TOMM34 gene encodes a cytosolic protein with chaperone-like activity that helps import some preproteins to the mitochondria by keeping them in an unfolded, import-compatible state. TOMM34 was found to be upregulated frequently in colorectal tumors, suggesting that it also has a role in the growth of cancer cells. In this context, TOMM34 is a potential target for novel anticancer drugs, and it might also be used in the diagnosis of colorectal cancer. Nuclear respiratory factors (NRFs) play an important role in governing the nuclear-mitochondrial interactions implicated in mitochondrial biogenesis. Our previous studies revealed that NRFs promote the expression of the major members of the mitochondrial transport machinery, TOMM70 and TOMM20. Here we report the existence of binding sites for NRF-1, Sp1, and NRF-2 in the 5′ region of the human TOMM34 gene. We determined the effects of mutations at these sites on promoter activity in HeLa S3 and A204 cells, in conjunction with chromatin immunoprecipitation experiments, electrophoretic mobility shift assays, and in vivo methylation analysis of the promoter region. We conclude that NRF-1 is the main transcription factor regulating the expression of TOMM34. Sp1 interacts with NRF-1 to stimulate the promoter's full activity.

KW - Mitochondrial import

KW - NRF-1

KW - Nuclear respiratory factor-1

KW - Sp1

KW - TOMM34

UR - http://www.scopus.com/inward/record.url?scp=39049159540&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=39049159540&partnerID=8YFLogxK

U2 - 10.1139/O07-151

DO - 10.1139/O07-151

M3 - Article

C2 - 18364745

AN - SCOPUS:39049159540

VL - 86

SP - 46

EP - 56

JO - Biochemistry and Cell Biology

JF - Biochemistry and Cell Biology

SN - 0829-8211

IS - 1

ER -