FEBS Letters
Volume 582, Issue 28 , Pages 3868-3874, 26 November 2008

A novel ING2 isoform, ING2b, synergizes with ING2a to prevent cell cycle arrest and apoptosis

Edited by Varda Rotter

  • Motoko Unoki

      Affiliations

    • Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, 37 Convent Dr., Bldg. 37, Rm. 3068, Bethesda, MD 20892, USA
    • Laboratory for Biomarker Development, The Institute of Physical and Chemical Research, RIKEN, Tokyo 108-8639, Japan
  • ,
  • Kensuke Kumamoto

      Affiliations

    • Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, 37 Convent Dr., Bldg. 37, Rm. 3068, Bethesda, MD 20892, USA
    • Second Department of Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan
  • ,
  • Ana I. Robles

      Affiliations

    • Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, 37 Convent Dr., Bldg. 37, Rm. 3068, Bethesda, MD 20892, USA
  • ,
  • Jiang Cheng Shen

      Affiliations

    • Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, 37 Convent Dr., Bldg. 37, Rm. 3068, Bethesda, MD 20892, USA
  • ,
  • Zhi-Ming Zheng

      Affiliations

    • HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA
  • ,
  • Curtis C. Harris

      Affiliations

    • Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, 37 Convent Dr., Bldg. 37, Rm. 3068, Bethesda, MD 20892, USA
    • Corresponding Author InformationCorresponding author. Fax: +1 301 496 0497.

Received 26 August 2008; received in revised form 10 October 2008; accepted 15 October 2008. published online 22 October 2008.

Abstract 

We identified a novel inhibitor of growth family member 2 (ING2) isoform, ING2b, which shares exon 2 with ING2a, but lacks the N-terminal p53 binding region. Contrary to ING2a, ING2b’s promoter has no p53 binding sites. Consistently, activation of p53 led to suppression of ING2a, leaving ING2b unaffected. Through isoform-specific targeting, we showed that ING2a knockdown suppressed cell growth only in the presence of p53, ING2b knockdown had no effect on cell growth, and knockdown of both induced cell cycle arrest and apoptosis independently of p53. ING2a and ING2b have compensatory roles that protect cells from cell cycle arrest and apoptosis and may be involved in development of chemotherapeutic resistance.

Abbreviation: ING, the inhibitor of growth

Keywords: ING2, ING2a, ING2b, p53, Isoform

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 The nucleotide sequence(s) reported in this paper has been submitted to the DDBJ/GenBankTM/EBI Data Bank with Accession Nos. AB196793 (human ING2b) and AB433625 (mouse ING2b).

PII: S0014-5793(08)00841-7

doi:10.1016/j.febslet.2008.10.024

FEBS Letters
Volume 582, Issue 28 , Pages 3868-3874, 26 November 2008