Nuclear accumulation of HMG2 protein is mediated by basic regions interspaced with a long DNA-binding sequence, and...

High mobility group 2 (HMG2) protein is ubiquitously distributed in the nucleus of higher eukaryotic cells. Accumulation of an HMG2-beta-galactosidase fusion protein expressed in COS-7 cells suggested active transport of HMG2 protein into the nucleus after translation in the cytoplasm. Deletion analysis of the HMG2 sequence in the HMG2-beta-galactosidase fusion protein indicated that basic regions interspaced with the long DNA-binding sequence in HMG2, called the HMG1/2 box, are necessary for the nuclear accumulation of HMG2. The close configuration of basic regions at both ends of the DNA-binding sequence in the tertiary structure may function as the nuclear localization signal. This novel nuclear localization signal structure is different from typical ones such as the single or bipartite basic cluster in many nuclear proteins. A portion of the HMG2 molecule remained in the cytoplasm after translation. Interspecies heterokaryon assay demonstrated that the acidic carboxyl terminus of HMG2 was necessary for retention of the protein in the nucleus.