The RNA-binding protein HuR regulates the stability and translation of numerous mRNAs encoding stress-response and proliferative proteins. Although its post-transcriptional influence has been linked primarily to its cytoplasmic translocation, here we report that moderate heat shock (HS) potently reduces HuR levels, thereby altering the expression of HuR target mRNAs. HS did not change HuR mRNA levels or de novo translation, but instead reduced HuR protein stability. Supporting the involvement of the ubiquitin-proteasome system in this process were results showing that (1) HuR was ubiquitinated in vitro and in intact cells, (2) proteasome inhibition increased HuR abundance after HS, and (3) the HuR kinase checkpoint kinase 2 protected against the loss of HuR by HS. Within a central, HS-labile approximately 110-amino-acid region, K182 was found to be essential for HuR ubiquitination and proteolysis as mutant HuR(K182R) was left virtually unubiquitinated and was refractory to HS-triggered degradation. Our findings reveal that HS transiently lowers HuR by proteolysis linked to K182 ubiquitination and that HuR reduction enhances cell survival following HS.
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http://dx.doi.org/10.1038/emboj.2009.67 | DOI Listing |
Adv Mater
December 2024
Extreme Materials Research Center, Korea Institute of Science and Technology, 5, Hwarang-ro 14-gil, Seoul, Seongbuk-gu, 02792, Republic of Korea.
Additive manufacturing has sought active and interactive means of creating predictable structures with diverse materials. Compared to such active manufacturing tools, current crystallization strategies remain in statistical and passive programs of crystals via macroscale thermodynamic controllers, commonly lacking active means to intervene in crystal growth in a spatiotemporal manner. Herein, a strategy toward active and interactive programming and reprogramming of crystals, realized by real-time tangible feedback on growing crystals by delicately controlling the degree of in-situ, localized photopolymerization of polymeric structures via additive manufacturing is presented.
View Article and Find Full Text PDFRNA Biol
December 2025
Department of Hepatobiliary and Pancreatic Surgery, Peking University First Hospital, Beijing, China.
The crosstalk between the tumour immune microenvironment (TIME) and tumour cells promote immune evasion and resistance to immunotherapy in gastrointestinal (GI) tumours. Post-transcriptional regulation of genes is pivotal to GI tumours progression, and RNA-binding proteins (RBPs) serve as key regulators via their RNA-binding domains. RBPs may exhibit either anti-tumour or pro-tumour functions by influencing the TIME through the modulation of mRNAs and non-coding RNAs expression, as well as post-transcriptional modifications, primarily N6-methyladenosine (mA).
View Article and Find Full Text PDFClin Sci (Lond)
December 2024
University of Utah Health, Salt Lake City, Utah, United States.
Septic acute kidney injury (AKI) is an important risk factor for developing chronic kidney disease (CKD). Hu antigen R (HuR) is recognized as a crucial modulator in inflammation. We hypothesized that elevated HuR contributes to the transition from septic AKI to CKD by promoting persistent inflammation and fibrosis, and inhibition of HuR may reverse septic kidney injury.
View Article and Find Full Text PDFJ Yeungnam Med Sci
December 2024
Division of Cardiology, Yeungnam University Medical Center, Daegu, Korea.
Background: Complete revascularization has demonstrated better outcomes in patients with acute myocardial infarction (AMI) and multivessel disease. However, in the case of left main (LM) culprit lesion AMI with multivessel disease, there is limited evidence to suggest that complete revascularization is better.
Methods: We reviewed 16,831 patients in the Korea Acute Myocardial Infarction Registry who were treated from July 2016 to June 2020, and 399 patients were enrolled with LM culprit lesion AMI treated with percutaneous coronary intervention.
Aesthetic Plast Surg
December 2024
Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 FOUR Project, Yonsei University College of Dentistry, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Korea.
Background: Genu varum, or bow-legged deformity, involves an outward curvature of the lower limbs, often creating a visible gap between the knees when the ankles are together. Traditionally treated with invasive surgical methods like high tibial osteotomy, genu varum correction now includes less invasive options for patients with mild to moderate deformities. This commentary explores a novel approach using hyaluronic acid (HA) filler to volumise the medial gastrocnemius muscle, thereby improving calf contour and stability without surgery.
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