Posttranscriptional orchestration of an anti-apoptotic program by HuR.
The RNA-binding protein HuR can stabilize and/or regulate the translation of target mRNAs, thereby affecting the cellular responses to immune, proliferative, and damaging agents. Here, we discuss emerging evidence that HuR elicits a broad anti-apoptotic function through its influence on the expression of multiple target mRNAs. HuR was previously shown to bind to the mRNA encoding the apoptosome inhibitor prothymosin a(ProT alpha) and enhanced its translation and cytoplasmic abundance. More recently, HuR was shown to increase the stability of a target mRNA encoding the pro-survival deacetylase SIRT1. The discovery that HuR likewise binds to and promotes the expression of mRNAs encoding Bcl-2 and Mcl-1, two major anti-apoptotic effectors, strongly supports HuR's role as a key upstream coordinator of a constitutive pro-survival program.
Abdelmohsen
Kotb
K
Laboratory of Cellular and Molecular Biology, National Institute on Aging-IRP, National Institutes of Health, Baltimore, Maryland 21224, USA.
Lal
Ashish
A
Kim
Hyeon Ho
HH
Gorospe
Myriam
M
D000954:Antigens, Surface / Q000502:physiology*; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics*; D002470:Cell Survival; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D019254:Genes, bcl-2; D006367:HeLa Cells; D006801:Humans; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D011485:Protein Binding; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D034622:RNA Interference / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000502:physiology*; D056564:Sirtuin 1; D037761:Sirtuins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D013947:Thymosin / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D011498:Protein Precursors; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C040782:prothymosin alpha; D013947:Thymosin; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D037761:Sirtuins