Since the cloning in 1997 of SEL1L, the human ortholog of the sel-1 gene of C. elegans, most studies have focused on its role in cancer progression and have provided significant evidences to link its increased expression to a decrease in tumor aggressiveness. SEL1L resides on a "Genome Desert area" on chromosome 14q24.3-31 and is highly conserved in evolution. The function of the SEL1L encoded protein is still very elusive although, several evidences from lower organisms indicate that it plays a major role in protein degradation using the ubiquitin-proteosome system. SEL1L has a very complex structure made up of modules: genomically it consists of 21 exons featuring several alternative transcripts encoding for putative protein isoforms. This structural complexity ensures protein flexibility and specificity, indeed the protein was found in different sub-cellular compartments and may turn on a particular transcript in response to specific stimuli. The overall architecture of SEL1L guarantees an exquisite regulation in the expression of the gene.
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http://dx.doi.org/10.1002/jcp.20574 | DOI Listing |
Obesity, insulin resistance, and a host of environmental and genetic factors can drive hyperglycemia, causing β-cells to compensate by increasing insulin production and secretion. In type 2 diabetes (T2D), β-cells under these conditions eventually fail. Rare β-cell diseases like congenital hyperinsulinism (HI) also cause inappropriate insulin secretion, and some HI patients develop diabetes.
View Article and Find Full Text PDFUnlabelled: The integrity of the hematopoietic stem cell (HSC) pool relies on efficient long-term self-renewal and the timely removal of damaged or differentiation-prone HSCs. Previous studies have demonstrated the PERK branch of the unfolded protein response (UPR) drives specific programmed cell death programs to maintain HSC pool integrity in response to ER stress. However, the role of PERK in regulating HSC fate remains unclear.
View Article and Find Full Text PDFWater Res
December 2024
Jiangsu Key Laboratory of Chemical Pollution Control and Resources Reuse, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Xiao Ling Wei 200, Nanjing 210094, Jiangsu, China. Electronic address:
High temperature (HT) shock is one of environmental stressors suppressing microalgal activities in microalgal wastewater bioremediation system. However, its inhibition mechanism and how to alleviate such suppression remain inadequately understood. This study confirmed a transient ferroptosis as a novel form of programmed cell death in a wastewater-indigenous Chlorella sp.
View Article and Find Full Text PDFFront Vet Sci
November 2024
Hubei Key Laboratory of Animal Nutrition and Feed Science, School of Animal Science and Nutritional Engineering, Wuhan Polytechnic University, Wuhan, China.
Nat Commun
October 2024
Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA.
Impaired secretion of an essential blood coagulation factor fibrinogen leads to hepatic fibrinogen storage disease (HFSD), characterized by the presence of fibrinogen-positive inclusion bodies and hypofibrinogenemia. However, the molecular mechanisms underlying the biogenesis of fibrinogen in the endoplasmic reticulum (ER) remain unexplored. Here we uncover a key role of SEL1L-HRD1 complex of ER-associated degradation (ERAD) in the formation of aberrant inclusion bodies, and the biogenesis of nascent fibrinogen protein complex in hepatocytes.
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