tretinoin and importazole

The RNA-binding protein HuR binds to elements rich in adenylate and uridylate (AU-rich elements) in target mRNAs and stabilizes them against degradation. The complete spectrum of genes whose expression is regulated by HuR and are the basis for the broad range of cellular functions of the protein is incompletely understood. We show that HuR controls the expression of multiple components of the nuclear import machinery. Consequently, HuR is crucial for the nuclear import of cellular retinoic acid-binding protein 2 (CRABP2), which delivers RA to the nuclear retinoic acid receptor (RAR) and whose mobilization to the nucleus is mediated by a 'classical-like' nuclear localization signal (NLS). HuR is also required for heregulin-induced nuclear translocation of the NFκB subunit p65, which contains both classical and non-canonical NLSs. HuR thus regulates the transcriptional activities of both RAR and NFκB. The observations reveal that HuR plays a central role in regulating nuclear import of proteins.

Topics: Active Transport, Cell Nucleus; Animals; Apoproteins; beta Karyopherins; Cell Nucleus; ELAV-Like Protein 1; Endoplasmic Reticulum; HEK293 Cells; Humans; Karyopherins; MCF-7 Cells; Mice; Nuclear Proteins; Quinazolines; Receptors, Retinoic Acid; RNA Stability; RNA, Messenger; Tretinoin