Spatial and temporal dynamics of two alternatively spliced regulatory factors, lens epithelium-derived growth factor (ledgf/p75) and p52, in the nucleus.

ABSTRACT

Regulatory factors, lens epithelium-derived growth factor (LEDGF)/p75 and p52, are generated from a single LEDGF gene by alternative splicing. They have identical amino acid residues between positions 1-325, but 205 and 8 of the remaining residues are different in LEDGF and p52, respectively. LEDGF promotes growth and survival of many cell types. It has an antiapoptotic function and is a weak general transcriptional co-activator. p52 is a transcriptional activator and an essential splicing factor. We investigated the spatial and temporal dynamics of LEDGF/p75 and p52, each being tagged with a fluorescent protein, during the cell cycles of CHO-K1, MCDK, and NRK cells in culture. Both LEDGF/p75 and p52 were localized predominantly in the nucleus. LEDGF/p75 was distributed diffusely in the nucleoplasm in the G1-phase and attached to chromatin heterogeneously during the G2 and M-phases of cells. In contrast, p52 was localized in the nuclear periphery during the G1-phase and formed a speckle pattern at the S-phase. It formed a cylindrical pattern around the chromosomes during the M-phases of cells. LEDGF and p52 on sister chromatids migrated into daughter cells. Thus, LEDGF/p75 and p52 are localized in distinct nuclear compartments where they can activate transcription or splicing of pre-mRNAs.