The tumor suppressor, p53 regulates the γA-crystallin gene during mouse lens development

X. H. Hu, Q. Nie, M. Yi, T. T. Li, Z. F. Wang, Z. X. Huang, X. D. Gong, L. Zhou, W. K. Ji, W. F. Hu, J. F. Liu, L. Wang, Z. Woodward, J. Zhu, Wen Bin Liu, Quan Dong Nguyen, David Wan Cheng Li

Research output: Contribution to journalArticle

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Abstract

The tumor suppressor, p53 regulates a large number of target genes to control cell proliferation and apoptosis. In addition, it is also implicated in the regulation of cell differentiation in muscle, the circulatory system and various carcinoma tissues. We have recently shown that p53 also controls lens differentiation. Regarding the mechanism, we reveal that p53 directly regulates several genes including c-Maf and Prox1, two important transcription factors for lens differentiation, and αA and βA3/A1, the lens differentiation markers. In the present study, we present evidence to show that the γA-crystallin gene distal promoter and the first intron also contain p53 binding sites and are capable of mediating p53 control during mouse lens development. First, gel mobility shifting assays revealed that the p53 protein in nuclear extracts from human lens epithelial cells (HLE) directly binds to the p53 binding sites present in the γA-crystallin gene. Second, the exogenous wild type p53 induces the dose-dependent expression of the luciferase reporter gene driven by the basic promoter containing the γA-crystallin gene p53 binding site. In contrast, the exogenous dominant negative mutant p53 causes a dose-dependent inhibition of the same promoter. Third, ChIP assays revealed that p53 binds to the γA-crystallin gene promoter in vivo. Finally, in the p53 knockout mouse lenses, the expression level of the γA-crystallin gene was found attenuated in comparison with that in the wild type mouse lenses. Together, our results reveal that p53 regulates γA-crystallin gene expression during mouse lens development. Thus, p53 directly regulates all 3 types of crystallin genes to control lens differentiation.

Original languageEnglish (US)
Pages (from-to)1197-1204
Number of pages8
JournalCurrent Molecular Medicine
Volume14
Issue number9
StatePublished - Jan 1 2014

Fingerprint

Crystallins
Lenses
Tumors
Genes
Neoplasms
Binding Sites
Assays
Differentiation Antigens
p53 Genes
Cell proliferation
Nuclear Proteins
Cardiovascular System
Luciferases
Reporter Genes
Gene expression
Knockout Mice
Introns
Muscle
Cell Differentiation
Transcription Factors

Keywords

  • Cataract
  • Gene regulation
  • Lens differentiation
  • p53
  • γA-crystallin gene

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Molecular Medicine

Cite this

Hu, X. H., Nie, Q., Yi, M., Li, T. T., Wang, Z. F., Huang, Z. X., ... Li, D. W. C. (2014). The tumor suppressor, p53 regulates the γA-crystallin gene during mouse lens development. Current Molecular Medicine, 14(9), 1197-1204.

The tumor suppressor, p53 regulates the γA-crystallin gene during mouse lens development. / Hu, X. H.; Nie, Q.; Yi, M.; Li, T. T.; Wang, Z. F.; Huang, Z. X.; Gong, X. D.; Zhou, L.; Ji, W. K.; Hu, W. F.; Liu, J. F.; Wang, L.; Woodward, Z.; Zhu, J.; Liu, Wen Bin; Nguyen, Quan Dong; Li, David Wan Cheng.

In: Current Molecular Medicine, Vol. 14, No. 9, 01.01.2014, p. 1197-1204.

Research output: Contribution to journalArticle

Hu, XH, Nie, Q, Yi, M, Li, TT, Wang, ZF, Huang, ZX, Gong, XD, Zhou, L, Ji, WK, Hu, WF, Liu, JF, Wang, L, Woodward, Z, Zhu, J, Liu, WB, Nguyen, QD & Li, DWC 2014, 'The tumor suppressor, p53 regulates the γA-crystallin gene during mouse lens development', Current Molecular Medicine, vol. 14, no. 9, pp. 1197-1204.
Hu XH, Nie Q, Yi M, Li TT, Wang ZF, Huang ZX et al. The tumor suppressor, p53 regulates the γA-crystallin gene during mouse lens development. Current Molecular Medicine. 2014 Jan 1;14(9):1197-1204.
Hu, X. H. ; Nie, Q. ; Yi, M. ; Li, T. T. ; Wang, Z. F. ; Huang, Z. X. ; Gong, X. D. ; Zhou, L. ; Ji, W. K. ; Hu, W. F. ; Liu, J. F. ; Wang, L. ; Woodward, Z. ; Zhu, J. ; Liu, Wen Bin ; Nguyen, Quan Dong ; Li, David Wan Cheng. / The tumor suppressor, p53 regulates the γA-crystallin gene during mouse lens development. In: Current Molecular Medicine. 2014 ; Vol. 14, No. 9. pp. 1197-1204.
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