Characterization of the Nuclear Export Signal of Human T-Cell Lymphotropic Virus Type 1 Rex Reveals that Nuclear Export Is Mediated by Position-Variable Hydrophobic Interactions

Abstract

The Rex protein of human T-cell lymphotropic virus type 1 (HTLV-1) mediates the cytoplasmic localization of incompletely spliced and unspliced viral RNAs (24). Rex is a member of a family of functionally related proteins, generally known as the Rev-like proteins, which are found in complex retroviruses. The Rev-like proteins have at least two essential domains with unique functions, (i) a specific RNA binding activity that interacts with structural response elements within the viral mRNAs and (ii) an effector or activation domain that facilitates interaction with endogenous pathways (12,17,20). The effector domain of human immunodeficiency virus type 1 (HIV-1) Rev has recently been demonstrated to be a nuclear export signal (NES) (9, 31). A NES in the cyclic AMP (cAMP)-dependent protein kinase inhibitor has a sequence similar to those of the effector domains of Rev-like proteins (31). Studies of chimeric proteins have demonstrated that the effector domains of many Rev-like proteins can act in a heterologous context. For example, the effector domains of viral Rev-like proteins can complement the function of an effector domain mutant of HIV-1 or visna virus Rev (10,12,19,29).The identified effector domains of Rev-like proteins fall into two classes, as shown in Fig.

Ajuba, a Novel LIM Protein, Interacts with Grb2, Augments Mitogen-Activated Protein Kinase Activity in Fibroblasts, and Promotes Meiotic Maturation of Xenopus Oocytes in a Grb2- and Ras-Dependent Manner

“…They also demonstrated that endogenous zyxin actually shuttles between the cytoplasm and nucleus. Ajuba also contains a strong putative NES, in a region of the protein complementary to the site of the NES present in zyxin (7,21). Interestingly, when we removed the pre-LIM domain of Ajuba, including a putative NES, and expressed this LIM-only isoform of Ajuba in fibroblast cells, we observed that a significant proportion of the LIM-only Ajuba was now present in the nucleus.…”

Post‐transcriptional regulation of gene expression by degradation of messenger RNAs

“…The NES-like sequence, composed of 3-5 hydrophobic amino acids with defined spacing (Bogerd et al, 1996;Kim et al, 1996), probably mediates the macromolecular traffic between the nucleus and cytoplasm. The nuclear export receptor Xpo1/CRM1 (Kudo et al, 1997) mediates the nuclear export of leucine-rich NES-containing proteins by binding directly to the NES (Fornerod et al, 1997;Fukuda et al, 1997;Stade et al, 1997).…”

Titration of cellular export factors, but not heteromultimerization, is the molecular mechanism of trans-dominant HTLV-1 Rex mutants

“…Regions which map to amino acids 57 ± 66 and 106 ± 124 were suggested to mediate Rex oligomerization (Bogerd and Greene, 1993;Weichselbraun et al, 1992a). A leucine-rich nuclear export signal (NES), identi®ed between amino acids 79 and 99, is essential for nucleo-cytoplasmic tra cking and thus Rex function (Bogerd et al, 1996;Kim et al, 1996;Palmeri and Malim, 1996;Weichselbraun et al, 1992b). Factors reported to interact directly with the NES domain include the eukaryotic initiation factor 5A (eIF-5A) (Katahira et al, 1995) and the export factor CRM1 (Fornerod et al, 1997;Fukuda et al, 1997;Ossareh-Nazari et al, 1997;Stade et al, 1997).…”