RNA-binding protein HuR regulates nuclear import of protein.
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.
Department of Cellular & Molecular Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Wei
W
Zhang
Department of Cellular & Molecular Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Amanda C
AC
Vreeland
Department of Cellular & Molecular Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA noyn@ccf.org.|Department of Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Noa
0000-0002-2404-1443
N
Noy
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D001059:Apoproteins / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D000067780:ELAV-Like Protein 1 / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D028884:Karyopherins / Q000378:metabolism; D061986:MCF-7 Cells; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology; D020871:RNA Stability / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology; D028961:beta Karyopherins / Q000378:metabolism
D001059:Apoproteins; D000067780:ELAV-Like Protein 1; D028884:Karyopherins; D009687:Nuclear Proteins; D011799:Quinazolines; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; C000597150:Tnpo1 protein, mouse; D028961:beta Karyopherins; C568452:importazole; C091775:ran-binding protein 1; C082928:retinoic acid binding protein II, cellular; D014212:Tretinoin
Cellular retinoic acid-binding protein; HuR; NFκB; Nuclear import; RNA stability; Retinoic acid