Activation of T lymphocytes by Ags or cytokines results in translocation of the transcription factors NF-kB, AP-1, NFAT, and STAT from the cytoplasm into the nucleus. The first step in the nuclear import process is recognition of a nuclear localization sequence (NLS) within the karyophilic protein by a cytoplasmic receptor such as the importin (karyopherin)-a subunit. The NLSs of NF-kB, AP-1, a...

RCC1 is the guanine nucleotide exchange factor for Ran GTPase. Generation of Ran-GTP by RCC1 on chromatin provides a spatial signal that directs nucleocytoplasmic transport, mitotic spindle assembly and nuclear envelope formation. We show that RCC1 is expressed in human cells as at least three isoforms, named RCC1alpha, RCC1beta and RCC1gamma, which are expressed at different levels in specific...

BACKGROUND Transport of macromolecules between the nucleus and cytoplasm of eukaryotic cells is mediated by nuclear import and export receptors. The receptors identified to date are members of a family of Ran GTPase-binding proteins whose founding member is importin-beta. Interaction between these receptors and their cargo is regulated by the GTP-bound form of Ran. Export complexes form and imp...

Bidirectional tRNA movement between the nucleus and the cytoplasm serves multiple biological functions. To gain a biochemical understanding of the mechanisms for tRNA subcellular dynamics, we developed in vivo β-importin complex coimmunoprecipitation (co-IP) assays using budding yeast. Our studies provide the first in vivo biochemical evidence that two β-importin family members, Los1 (exportin-...

The importin-β family members (karyopherins) mediate the majority of nucleocytoplasmic transport. Msn5 and Los1, members of the importin-β family, function in tRNA nuclear export. tRNAs move bidirectionally between the nucleus and the cytoplasm. Nuclear tRNA accumulation occurs upon amino acid (aa) or glucose deprivation. To understand the mechanisms regulating tRNA subcellular trafficking, we ...

Retroviral Gag polyproteins coopt host factors to traffic from cytosolic ribosomes to the plasma membrane, where virions are released. Before membrane transport, the multidomain Gag protein of Rous sarcoma virus (RSV) undergoes importin-mediated nuclear import and CRM1-dependent nuclear export, an intrinsic step in the assembly pathway. Transient nuclear trafficking of Gag is required for effic...

Expression of prohibitin 1 (PHB), a multi-functional protein in the cell, is decreased during inflammatory bowel disease (IBD). Little is known regarding the regulation and role of PHB during intestinal inflammation. We examined the effect of tumor necrosis factor alpha (TNF), a cytokine that plays a central role in the pathogenesis of IBD, on PHB expression and the effect of sustained PHB exp...

Targeting of most nuclear proteins to the cell nucleus is initiated by interaction between the classical nuclear localization signals (NLSs) contained within them and the importin NLS receptor complex. We have recently delineated a novel 38 amino acid transport signal in the hnRNP A1 protein, termed M9, which confers bidirectional transport across the nuclear envelope. We show here that M9-medi...

A general paradigm for nuclear transport was established primarily through studies of protein import and export. Until recently, this paradigm was generally presumed also to apply to the process of RNA export from the nucleus. In particular, it was assumed that general mRNA export was mediated by one or more transport receptors of the importin-β family and that the RanGTP/GDP gradient was requi...