@article {1627,
	title = {RNA-binding proteins La and HuR cooperatively modulate translation repression of PDCD4 mRNA [Mass Spectrometry Facility - Proteomics]},
	journal = {J Biol Chem .},
	volume = {doi: 10.1074/jbc.RA120.014894. Online ahead of print.},
	year = {2020},
	month = {12/2020},
	abstract = {<p><span style="color: rgb(33, 33, 33); font-family: BlinkMacSystemFont, -apple-system, \&quot;Segoe UI\&quot;, Roboto, Oxygen, Ubuntu, Cantarell, \&quot;Fira Sans\&quot;, \&quot;Droid Sans\&quot;, \&quot;Helvetica Neue\&quot;, sans-serif; font-size: 16px;">Post-transcriptional regulation of gene expression plays a critical role in controlling the inflammatory response. An uncontrolled inflammatory response results in chronic inflammation, often leading to tumorigenesis. Programmed cell death 4 (PDCD4) is a pro-inflammatory tumor-suppressor gene which helps to prevent the transition from chronic inflammation to cancer. PDCD4 mRNA translation is regulated by an interplay between the oncogenic microRNA miR-21 and the RNA-binding protein (RBP) HuR in response to LPS stimulation, but the role of other regulatory factors remain unknown. Here we report that the RBP Lupus antigen (La) interacts with the 3{\textquoteright}UTR of PDCD4 mRNA and prevents miR-21-mediated translation repression. While LPS causes nuclear-cytoplasmic translocation of HuR, it enhances cellular La expression. Remarkably, La and HuR were found to bind cooperatively to the PDCD4 mRNA and mitigate miR-21-mediated translation repression. The cooperative action of La and HuR reduced cell proliferation and enhanced apoptosis, reversing the pro-oncogenic function of miR-21. Together, these observations demonstrate a cooperative interplay between two RBPs, triggered differentially by the same stimulus, which exerts a synergistic effect on PDCD4 expression and thereby helps maintain a balance between inflammation and tumorigenesis.</span></p>
},
	author = {Kumar, Ravi and Poria, Dipak Kumar and Ray,  Partho Sarothi}
}
