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PMID:14645522

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Citation

Tessari, MA, Gostissa, M, Altamura, S, Sgarra, R, Rustighi, A, Salvagno, C, Caretti, G, Imbriano, C, Mantovani, R, Del Sal, G, Giancotti, V and Manfioletti, G (2003) Transcriptional activation of the cyclin A gene by the architectural transcription factor HMGA2. Mol. Cell. Biol. 23:9104-16

Abstract

The HMGA2 protein belongs to the HMGA family of architectural transcription factors, which play an important role in chromatin organization. HMGA proteins are overexpressed in several experimental and human tumors and have been implicated in the process of neoplastic transformation. Hmga2 knockout results in the pygmy phenotype in mice and in a decreased growth rate of embryonic fibroblasts, thus indicating a role for HMGA2 in cell proliferation. Here we show that HMGA2 associates with the E1A-regulated transcriptional repressor p120(E4F), interfering with p120(E4F) binding to the cyclin A promoter. Ectopic expression of HMGA2 results in the activation of the cyclin A promoter and induction of the endogenous cyclin A gene. In addition, chromatin immunoprecipitation experiments show that HMGA2 associates with the cyclin A promoter only when the gene is transcriptionally activated. These data identify the cyclin A gene as a cellular target for HMGA2 and, for the first time, suggest a mechanism for HMGA2-dependent cell cycle regulation.

Links

PubMed PMC309667

Keywords

Adenovirus E4 Proteins/chemistry; Adenovirus E4 Proteins/genetics; Adenovirus E4 Proteins/metabolism; Animals; Base Sequence; Binding Sites; CHO Cells; Cell Cycle; Cell Line; Cell Transformation, Neoplastic; Cricetinae; Cyclin A/genetics; DNA, Complementary/genetics; HMGA2 Protein/genetics; HMGA2 Protein/metabolism; Humans; Mice; Models, Biological; NIH 3T3 Cells; Promoter Regions, Genetic; Repressor Proteins/chemistry; Repressor Proteins/genetics; Repressor Proteins/metabolism; Transcriptional Activation; Zinc Fingers

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:HMGA2

enables

GO:0061629: RNA polymerase II-specific DNA-binding transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q66K89

F

Seeded From UniProt

complete

MOUSE:HMGA2

involved_in

GO:0010564: regulation of cell cycle process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:E4F1

involved_in

GO:0051726: regulation of cell cycle

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:E4F1

enables

GO:0061629: RNA polymerase II-specific DNA-binding transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P52926

F

Seeded From UniProt

complete

MOUSE:E4F1

involved_in

GO:0010564: regulation of cell cycle process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:HMGA2

enables

GO:0070742: C2H2 zinc finger domain binding

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:HMGA2

enables

GO:0008134: transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q66K89

F

Seeded From UniProt

complete

HUMAN:HMGA2

involved_in

GO:0010564: regulation of cell cycle process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:HMGA2

enables

GO:0035497: cAMP response element binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:HMGA2

involved_in

GO:0043392: negative regulation of DNA binding

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:HMGA2

involved_in

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:E4F1

involved_in

GO:0071850: mitotic cell cycle arrest

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:E4F1

involved_in

GO:0000122: negative regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:E4F1

involved_in

GO:0010564: regulation of cell cycle process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:E4F1

enables

GO:0035497: cAMP response element binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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