Transformation by the Bmi-1 oncoprotein correlates with its subnuclear localization but not its transcriptional suppression activity

Kenneth J Cohen, Joseph S. Hanna, Julia E. Prescott, Chi V. Dang

Research output: Contribution to journalArticle

Abstract

The bmi-1 oncogene cooperates with c-myc in transgenic mice, resulting in accelerated lymphoma development. Altering the expression of Bmi-1 affects normal embryogenesis. The protein product of brai-1 is homologous to certain Drosophila Polycomb group proteins that regulate homeotic gene expression through alteration of chromatin structure. Chimeric LexA-Bmi-1 protein has previously been shown to repress transcription. How Bmi-1 functions in embryogenesis and whether this relates to the ability of Bmi-1 to mediate cellular transformation is unknown. We demonstrate here that Bmi-1 is able to transform rodent fibroblasts in vitro, providing a system that has allowed us to correlate its molecular properties with its ability to transform cells. We map functional domains of Bmi-1 involved in transcriptional suppression by using the GAL4 chimetic transcriptional regulator system. Deletion analysis shows that the centrally located helix-turn-helix-turn-helix-turn (HTHTHT) motif is necessary for transcriptional suppression whereas the N-terminal RING finger domain is not required. We demonstrate that nuclear localization requires KRMK (residues 230 to 233) and that the absence of nuclear entry ablates transformation. In addition, we find that the subnuclear localization of wild-type Bmi-1 to the rim of the nucleus requires the RING finger domain and correlates with its ability to transform. Our studies with Bmi-1 deletion mutants suggest that the ability of Bmi-1 to mediate cellular transformation correlates with its unique subnuclear localization but not its transcriptional suppression activity.

Original languageEnglish (US)
Pages (from-to)5527-5535
Number of pages9
JournalMolecular and Cellular Biology
Volume16
Issue number10
StatePublished - 1996

Fingerprint

RING Finger Domains
Oncogene Proteins
Embryonic Development
Helix-Turn-Helix Motifs
Polycomb-Group Proteins
Homeobox Genes
Oncogenes
Transgenic Mice
Chromatin
Rodentia
Lymphoma
Proteins
Fibroblasts
Gene Expression

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Transformation by the Bmi-1 oncoprotein correlates with its subnuclear localization but not its transcriptional suppression activity. / Cohen, Kenneth J; Hanna, Joseph S.; Prescott, Julia E.; Dang, Chi V.

In: Molecular and Cellular Biology, Vol. 16, No. 10, 1996, p. 5527-5535.

Research output: Contribution to journalArticle

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