Title

Intranuclear trafficking of transcription factors: implications for biological control

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Cell Biology and Cancer Center

Date

6-23-2000

Document Type

Article

Medical Subject Headings

Biological Transport; Cell Nucleus; Chromatin; Core Binding Factor Alpha 2 Subunit; DNA-Binding Proteins; *Gene Expression Regulation; Humans; Macromolecular Substances; Models, Biological; Mutation; Neoplasms; Nuclear Envelope; Nuclear Matrix; Nuclear Proteins; Protein Structure, Tertiary; *Proto-Oncogene Proteins; Transcription Factors

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

The subnuclear organization of nucleic acids and cognate regulatory factors suggests that there are functional interrelationships between nuclear structure and gene expression. Nuclear proteins that are localized in discrete domains within the nucleus include the leukemia-associated acute myelogenous leukemia (AML) and promyelocytic leukemia (PML) factors, the SC-35 RNA-processing factors, nucleolar proteins and components of both transcriptional and DNA replication complexes. Mechanisms that control the spatial distribution of transcription factors within the three-dimensional context of the nucleus may involve the sorting of regulatory information, as well as contribute to the assembly and activity of sites that support gene expression. Molecular, cellular, genetic and biochemical approaches have identified distinct protein segments, termed intranuclear-targeting signals, that are responsible for directing regulatory factors to specific subnuclear sites. Gene rearrangements that remove or alter intranuclear-targeting signals are prevalent in leukemias and have been linked to altered localization of regulatory factors within the nucleus. These modifications in the intranuclear targeting of transcription factors might abrogate fidelity of gene expression in tumor cells by influencing the spatial organization and/or assembly of machineries involved in the synthesis and processing of gene transcripts.

Rights and Permissions

Citation: J Cell Sci. 2000 Jul;113 ( Pt 14):2527-33.

Related Resources

Link to Article in PubMed