Chaperone Hsp27, a novel subunit of AUF1 protein complexes, functions in AU-rich element-mediated mRNA decay.
Controlled, transient cytokine production by monocytes depends heavily upon rapid mRNA degradation, conferred by 3' untranslated region-localized AU-rich elements (AREs) that associate with RNA-binding proteins. The ARE-binding protein AUF1 forms a complex with cap-dependent translation initiation factors and heat shock proteins to attract the mRNA degradation machinery. We refer to this protein assembly as the AUF1- and signal transduction-regulated complex, ASTRC. Rapid degradation of ARE-bearing mRNAs (ARE-mRNAs) requires ubiquitination of AUF1 and its destruction by proteasomes. Activation of monocytes by adhesion to capillary endothelium at sites of tissue damage and subsequent proinflammatory cytokine induction are prominent features of inflammation, and ARE-mRNA stabilization plays a critical role in the induction process. Here, we demonstrate activation-induced subunit rearrangements within ASTRC and identify chaperone Hsp27 as a novel subunit that is itself an ARE-binding protein essential for rapid ARE-mRNA degradation. As Hsp27 has well-characterized roles in protein ubiquitination as well as in adhesion-induced cytoskeletal remodeling and cell motility, its association with ASTRC may provide a sensing mechanism to couple proinflammatory cytokine induction with monocyte adhesion and motility.
Department of Molecular Genetics, Microbiology and Immunology, UMDNJ-Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, USA.
Kristina S
KS
Sinsimer
Frances M
FM
Gratacós
Anna M
AM
Knapinska
Jiebo
J
Lu
Christopher D
CD
Krause
Alexandria V
AV
Wierzbowski
Lauren R
LR
Maher
Shannon
S
Scrudato
Yonaira M
YM
Rivera
Swati
S
Gupta
Danielle K
DK
Turrin
Mary Pauline
MP
De La Cruz
Sidney
S
Pestka
Gary
G
Brewer
D045744:Cell Line, Tumor; D002470:Cell Survival; D031541:Fluorescence Resonance Energy Transfer; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism*; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000378:metabolism*; D006801:Humans; D018832:Molecular Chaperones; D046912:Multiprotein Complexes / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D011485:Protein Binding; D021122:Protein Subunits / Q000378:metabolism*; D020871:RNA Stability; D038621:Regulatory Sequences, Ribonucleic Acid / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
C000630986:HNRNPD protein, human; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; D018832:Molecular Chaperones; D046912:Multiprotein Complexes; D009363:Neoplasm Proteins; D021122:Protein Subunits; D038621:Regulatory Sequences, Ribonucleic Acid; D014409:Tumor Necrosis Factor-alpha