AI Article Synopsis
- HFE, a nonclassical MHC-I molecule, plays a key role in controlling iron levels in cells, but its regulation is not fully understood.
- K5, an E3 ubiquitin ligase from KSHV, targets HFE for degradation through polyubiquitination, which leads to its sorting from endosomes to lysosomes.
- In KSHV-infected BC-3 cells, HFE undergoes rapid degradation upon virus reactivation, indicating both K5 and an endogenous E3 ligase are involved in regulating HFE to maintain iron homeostasis.
Article Abstract
The nonclassical MHC class I-related (MHC-I) molecule HFE controls cellular iron homeostasis by a mechanism that has not been fully elucidated. We examined the regulation of HFE by K5, the E3 ubiquitin ligase encoded by Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8), that is known to down-regulate classical MHC-I. K5 down-regulated HFE efficiently, using polyubiquitination of the membrane proximal lysine in the HFE cytoplasmic tail (K331), to target the molecule for degradation via ESCRT1/TSG101-dependent sorting from endosomes to multivesicular bodies (MVBs)/lysosomes. In the primary effusion lymphoma cell line BC-3, which carries latent KSHV, HFE was degraded rapidly upon virus reactivation. HFE was ubiquitinated on lysine-331 in unactivated BC-3 cells, conditions where K5 was not detectable, consistent with an endogenous E3 ubiquitin ligase controlling HFE expression. The results show regulated expression of HFE by ubiquitination, consistent with a role in cellular iron homeostasis, a molecular mechanism targeted by KSHV to achieve a positive iron balance.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2941293 | PMC |
| http://dx.doi.org/10.1073/pnas.1003421107 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Feed efficiency and resilience in dairy ewes subjected to a nutritional challenge.
J Dairy Sci
January 2025
Instituto de Ganadería de Montaña (CSIC-University of León), Finca Marzanas s/n, 24346 Grulleros, León, Spain.
It is currently uncertain how selection of more efficient animals might impact other traits such as resilience (which, in this context, is defined as the ability of an animal to sustain or revert quickly to its previous production level and health status after a disturbance), especially in small ruminants. However, improving, or at least maintaining, resilience is of utmost importance to ensure livestock production in the face of external perturbances, which are expected to become more prevalent in the near future due to climate change and global instability. This study was conducted to investigate whether a nutritional challenge consisting of animals receiving only 70% of their voluntary feed intake (DMI) for 26 d, might differentially affect the response of high- and low-feed efficiency (FE) sheep.
View Article and Find Full Text PDFSemantic aware enhanced event causality identification.
Sci Rep
December 2024
School of Computer Science and Technology, Xinjiang University, Urumqi, 830017, China.
Event Causality Identification (ECI) aims to predict causal relations between events in a text. Existing research primarily focuses on leveraging external knowledge such as knowledge graphs and dependency trees to construct explicit structured features to enrich event representations. However, this approach underestimates the semantic features of the original input sentences and performs poorly in capturing implicit causal relations.
View Article and Find Full Text PDFYersiniosis has a causal relationship with hereditary hemochromatosis (HH). Physicians should have a high index of suspicion for the diagnosis of HH when approaching a patient with yersiniosis in the setting of high ferritin levels and increased iron saturation. Yersiniosis serves as a precursor for the diagnosis of HH.
View Article and Find Full Text PDFNon-HFE Hemochromatosis in the Context of β-Thalassemia Trait: A Case Study on Iron Overload Dysregulation.
Cureus
November 2024
Internal Medicine, Creighton University School of Medicine, St. Joseph's Hospital and Medical Center, Phoenix, USA.
Thalassemia and hemochromatosis are two distinct conditions that involve dysregulation of iron metabolism, though their origin, clinical presentations, and treatments differ. This case represents a patient with incidentally discovered microcytic anemia due to β-thalassemia trait and non- hemochromatosis. It discusses the potential synergistic effect of these two diseases on iron overload and highlights the need for further testing to determine hereditary versus secondary causes of hemochromatosis.
View Article and Find Full Text PDFDirect Assessment of Hereditary Hemochromatosis in Preimplantation Genetic Testing.
F S Sci
December 2024
Orchid Health Genomic Lab, Durham, NC, 27703. Electronic address:
Objective: Hereditary hemochromatosis (HH) is a common genetic disorder characterized by iron overload, which, if undiagnosed, can lead to severe organ damage. There are four types of HH. Type 1 HH, the most common form, is primarily caused by a common variant in Western Europe (p.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!