Cell growth suppression by thanatos-associated protein 11(THAP11) is mediated by transcriptional downregulation of c-Myc

C. Y. Zhu, C. Y. Li, Y. Li, Y. Q. Zhan, Y. H. Li, C. W. Xu, W. X. Xu, Hui (Herb) Sun, X. M. Yang

Research output: Contribution to journalArticle

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Abstract

Thanatos-associated proteins (THAPs) are zinc-dependent, sequence-specific DNA-binding factors involved in cell proliferation, apoptosis, cell cycle, chromatin modification and transcriptional regulation. THAP11 is the most recently described member of this human protein family. In this study, we show that THAP11 is ubiquitously expressed in normal tissues and frequently downregulated in several human tumor tissues. Overexpression of THAP11 markedly inhibits growth of a number of different cells, including cancer cells and non-transformed cells. Silencing of THAP11 by RNA interference in HepG2 cells results in loss of cell growth repression. These results suggest that human THAP11 may be an endogenous physiologic regulator of cell proliferation. We also provide evidence that the function of THAP11 is mediated by its ability to repress transcription of c-Myc. Promoter reporter assays indicate a DNA binding-dependent c-Myc transcriptional repression. Chromatin immunoprecipitations and EMSA assay suggest that THAP11 directly binds to the c-Myc promoter. The findings that expression of c-Myc rescues significantly cells from THAP11-mediated cell growth suppression and that THAP11 expression only slightly inhibits c-Myc null fibroblasts cells growth reveal that THAP11 inhibits cell growth through downregulation of c-Myc expression. Taken together, these suggest that THAP11 functions as a cell growth suppressor by negatively regulating the expression of c-Myc.

Original languageEnglish (US)
Pages (from-to)395-405
Number of pages11
JournalCell Death and Differentiation
Volume16
Issue number3
DOIs
StatePublished - 2009
Externally publishedYes

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Down-Regulation
Growth
Proteins
Cell Proliferation
Null Lymphocytes
Chromatin Immunoprecipitation
Hep G2 Cells
RNA Interference
Chromatin
Zinc
Neoplasms
Cell Cycle
Fibroblasts
Cell Count
Apoptosis
DNA

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Cell growth suppression by thanatos-associated protein 11(THAP11) is mediated by transcriptional downregulation of c-Myc. / Zhu, C. Y.; Li, C. Y.; Li, Y.; Zhan, Y. Q.; Li, Y. H.; Xu, C. W.; Xu, W. X.; Sun, Hui (Herb); Yang, X. M.

In: Cell Death and Differentiation, Vol. 16, No. 3, 2009, p. 395-405.

Research output: Contribution to journalArticle

Zhu, C. Y. ; Li, C. Y. ; Li, Y. ; Zhan, Y. Q. ; Li, Y. H. ; Xu, C. W. ; Xu, W. X. ; Sun, Hui (Herb) ; Yang, X. M. / Cell growth suppression by thanatos-associated protein 11(THAP11) is mediated by transcriptional downregulation of c-Myc. In: Cell Death and Differentiation. 2009 ; Vol. 16, No. 3. pp. 395-405.
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