Intranuclear trafficking of transcription factors: implications for biological control

The subnuclear organization of nucleic acids and cognate regulatory factors suggests that there are functional interrelationships between nuclear stru cture and gene expression. Nuclear proteins that are localized in discrete domains within the nucleus include the leukemia-associated acute myelogenou s leukemia (AML) and promyelocytic leukemia (PML) factors, the SC-35 RNA-pr ocessing factors, nucleolar proteins and components of both transcriptional and DNA replication complexes. Mechanisms that control the spatial distrib ution of transcription factors within the three-dimensional context of the nucleus may involve the sorting of regulatory information, as well as contr ibute to the assembly and activity of sites that support gene expression. M olecular, cellular genetic and biochemical approaches have identified disti nct protein segments, termed intranuclear-targeting signals, that are respo nsible for directing regulatory factors to specific subnuclear sites. Gene rearrangements that remove or alter intranuclear-targeting signals are prev alent in leukemias and have been linked to altered localization of regulato ry factors within the nucleus. These modifications in the intranuclear targ eting of transcription factors might abrogate fidelity of gene expression i n tumor cells by influencing the spatial organization and/or assembly of ma chineries involved in the synthesis and processing of gene transcripts.