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Molecular Characterization of Integr...

Wong, Albert.

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Molecular Characterization of Integrin-Induced mRNA Stabilization in T Cells.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Molecular Characterization of Integrin-Induced mRNA Stabilization in T Cells./
作者:	Wong, Albert.
面頁冊數:	69 p.
附註:	Source: Dissertation Abstracts International, Volume: 76-11(E), Section: B.
Contained By:	Dissertation Abstracts International76-11B(E).
標題:	Cellular biology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3663681
ISBN:	9781321965469

Molecular Characterization of Integrin-Induced mRNA Stabilization in T Cells.
Wong, Albert.

Molecular Characterization of Integrin-Induced mRNA Stabilization in T Cells. - 69 p.

Source: Dissertation Abstracts International, Volume: 76-11(E), Section: B.

Thesis (Ph.D.)--Yale University, 2015.

Leukocyte integrin lymphocyte function-associated antigen-1 (LFA-1) engagement during T cell activation plays a critical role in forming the immunological synapse1, transducing coactivatory signals that, among other effects, lead to significant changes in proinflammatory messenger RNA (mRNA) half-life and gene expression2. Specifically, LFA-1 activates the p38-MK2 pathway, which in turn causes Hu protein R (HuR), a ubiquitously expressed mRNA-binding protein, to translocate to the cytoplasm, where it binds to and stabilizes intrinsically labile 3' untranslated region (UTR) adenylateuridylate (AU)-rich element (ARE)-bearing mRNAs. However, the molecular mechanism by which MK2 controls HuR localization is not known. Here, I show that T cell HuR is a member of a constitutive nuclear protein complex comprised of heterogeneous nuclear ribonucleoproteins (hnRNPs) Al, C, H1 and K. hnRNPs C, H1 and K are basal negative regulators, retaining HuR in the nucleus and preventing it from translocating and stabilizing labile cytokine transcripts. LFA-1 engagement results in p38 and MK2 activation; activated MK2 in turn associates with and phosphorylates hnRNPA1 at its C-terminal F-peptide. This induces HuR to dissociate from the basal hnRNP complex, allowing it to translocate to the cytoplasm and extend the half-life of proinflammatory transcripts such as interferon (IFN)-gamma, interleukin (IL)-8 and tumor necrosis factor (TNF)a. These findings indicate that the fine tuning of inflammatory cytokine expression in T cells is dynamically controlled by a cell adhesion-modulated alteration in an intricate collection of hnRNPs, which both positively and negatively regulate HuR. More broadly, these results advance the understanding of T cell biology in general and may have longterm implications for the development of effective, targeted therapeutics for the treatment of diseases caused by aberrant or excessive T cell activity.

ISBN: 9781321965469Subjects--Topical Terms:

3172791
Cellular biology.

Molecular Characterization of Integrin-Induced mRNA Stabilization in T Cells.
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