THE SECOND AT-HOOK OF THE ARCHITECTURAL TRANSCRIPTION FACTOR HMGA2 IS DETERMINANT FOR NUCLEAR LOCALIZATION AND FUNCTION

Cattaruzzi, G; Altamura, S; Tessari, Ma; Giancotti, V; Pucillo, C; Manfioletti, Guidalberto

doi:10.1093/nar/gkl1106

Here, we report the identification and characterization of a nuclear localization signal (NLS) for HMGA2, a member of the HMGA family. The NLS overlaps with the second of the three AT-hooks, the DNA-binding domains characteristic for this group of proteins. The functionality of this NLS was demonstrated by its ability to target a heterologous β-galactosidase/green fluorescent protein fusion protein to the nucleus. Mutations to alanine of basic residues within the second AT-hook resulted in inhibition of HMGA2 nuclear localization and impairment of its function in activating the cyclin A promoter. In addition, HMGA2 was shown to directly interact with the nuclear import receptor importin-α2 via the second AT-hook. HMGA proteins are overexpressed and rearranged in a variety of tumors; our findings can thus help elucidating their role in neoplastic transformation.

Titolo:	THE SECOND AT-HOOK OF THE ARCHITECTURAL TRANSCRIPTION FACTOR HMGA2 IS DETERMINANT FOR NUCLEAR LOCALIZATION AND FUNCTION
Autori:	CATTARUZZI G ALTAMURA S TESSARI MA GIANCOTTI V PUCILLO C MANFIOLETTI, GUIDALBERTO mostra contributor esterni nascondi contributor esterni
Data di pubblicazione:	2007
Rivista:	NUCLEIC ACIDS RESEARCH
Abstract:	Here, we report the identification and characterization of a nuclear localization signal (NLS) for HMGA2, a member of the HMGA family. The NLS overlaps with the second of the three AT-hooks, the DNA-binding domains characteristic for this group of proteins. The functionality of this NLS was demonstrated by its ability to target a heterologous β-galactosidase/green fluorescent protein fusion protein to the nucleus. Mutations to alanine of basic residues within the second AT-hook resulted in inhibition of HMGA2 nuclear localization and impairment of its function in activating the cyclin A promoter. In addition, HMGA2 was shown to directly interact with the nuclear import receptor importin-α2 via the second AT-hook. HMGA proteins are overexpressed and rearranged in a variety of tumors; our findings can thus help elucidating their role in neoplastic transformation.
Handle:	http://hdl.handle.net/11368/1696757
Digital Object Identifier (DOI):	http://dx.doi.org/10.1093/nar/gkl1106
Appare nelle tipologie:	1.1 Articolo in Rivista

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