Molecular regulation of SREBP function: the Insig-SCAP connection and isoform-specific modulation of lipid synthesis

2004 ◽  
Vol 82 (1) ◽  
pp. 201-211 ◽  
Author(s):  
Ruth McPherson ◽  
Andre Gauthier
Keyword(s):  
Acid Metabolism ◽  
Regulatory Element ◽  
Lipid Synthesis ◽  
Molecular Regulation ◽  
New Information ◽  
Ubiquitin Proteasome ◽  
Sterol Regulatory Element ◽  
Membrane Bound ◽  
Proteasome Pathway

Sterol regulatory element binding proteins (SREBPs) are a family of membrane-bound transcription factors that play a unique and fundamental role in both cholesterol and fatty acid metabolism, relevant to human disease. There are three SREBPs that regulate the expression of over 30 genes. SREBPs are subject to regulation at three levels: proteolytic cleavage, rapid degradation by the ubiquitin-proteasome pathway, and sumoylation. Recently, there have been exciting advances in our understanding of the molecular mechanism of SREBP trafficking and processing with new information on the role of insulin-induced genes and the differential role and regulation of SREBP-1c and -2, which may ultimately lead to novel strategies for the treatment of dyslipidemia and insulin resistance.Key words: SREBP, Insig, SCAP, cholesterol synthesis, lipid metabolism.

Role of molecular chaperones in steroid receptor action

2004 ◽  
Vol 40 ◽  
pp. 41-58 ◽  
Author(s):  
William B Pratt ◽  
Mario D Galigniana ◽  
Yoshihiro Morishima ◽  
Patrick J M Murphy
Keyword(s):  
Transcriptional Activation ◽  
Protein Trafficking ◽  
Steroid Receptors ◽  
Transcriptional Regulatory ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
Receptor Action ◽  
Binding Cleft ◽  
Hsp 90

Unliganded steroid receptors are assembled into heterocomplexes with heat-shock protein (hsp) 90 by a multiprotein chaperone machinery. In addition to binding the receptors at the chaperone site, hsp90 binds cofactors at other sites that are part of the assembly machinery, as well as immunophilins that connect the assembled receptor-hsp90 heterocomplexes to a protein trafficking pathway. The hsp90-/hsp70-based chaperone machinery interacts with the unliganded glucocorticoid receptor to open the steroid-binding cleft to access by a steroid, and the machinery interacts in very dynamic fashion with the liganded, transformed receptor to facilitate its translocation along microtubular highways to the nucleus. In the nucleus, the chaperone machinery interacts with the receptor in transcriptional regulatory complexes after hormone dissociation to release the receptor and terminate transcriptional activation. By forming heterocomplexes with hsp90, the chaperone machinery stabilizes the receptor to degradation by the ubiquitin-proteasome pathway of proteolysis.

scholarly journals Ubiquitin Proteasome Pathway annotation in Diaphorina citri can reveal potential targets for RNAi based pest management

2021 ◽  
Author(s):  
Will Tank ◽  
Teresa Shippy ◽  
Amanda Thate ◽  
Crissy Massimino ◽  
Prashant S Hosmani ◽  
...  
Keyword(s):  
Management Strategies ◽  
Bacterial Pathogen ◽  
Diaphorina Citri ◽  
Ubiquitin Proteasome Pathway ◽  
Citrus Greening Disease ◽  
Pathway Annotation ◽  
New Information ◽  
Genomic Studies ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway

Ubiquitination is an ATP-dependent process that targets proteins for degradation by the proteasome. In this study, we annotated 15 genes from the ubiquitin-proteasome pathway in the Asian citrus psyllid, Diaphorina citri. This psyllid vector has come to prominence in the last decade due to its role in the transmission of the devastating bacterial pathogen, Candidatus Liberibacter asiaticus (CLas). Infection of citrus crops by this pathogen causes Huanglongbing (HLB or citrus greening disease) and results in the eventual death of citrus trees. The identification and correct annotation of these genes in D. citri will be useful for functional genomic studies that aid in the development of RNAi-based management strategies aimed at reducing the spread of HLB. Investigating the effects of CLas infection on the expression of ubiquitin-proteasome pathway genes may provide new information regarding the role that these genes play in the acquisition and transmission of CLas by D. citri.

Abstract 44: TAK1 Regulates Caspase 8 Activation and Necroptotic Signaling via Multiple Cell Death Checkpoints

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Xaioyun Guo ◽  
Haifeng Yin ◽  
Yi Chen ◽  
Lei Li ◽  
Jing Li ◽  
...  
Keyword(s):  
Cell Death ◽  
Adaptor Protein ◽  
Regulatory Mechanisms ◽  
Caspase 8 ◽  
Ubiquitin Proteasome Pathway ◽  
Pathological Conditions ◽  
Ubiquitin Proteasome ◽  
Multiple Cell ◽  
Proteasome Pathway

Necroptosis has emerged as a new form of programmed cell death implicated in a number of pathological conditions such as ischemic injury, neurodegenerative disease, and viral infection. Recent studies indicate that TGFβ-activated kinase 1 (TAK1) is nodal regulator of necroptotic cell death, but the underlying molecular regulatory mechanisms remain elusive. Here we reported that TAK1 regulates necroptotic signaling as well as caspase 8 activation through both NFκB-dependent and -independent mechanisms. Inhibition of TAK1 promoted TNFα-induced necroptosis through the induction of RIP1 phosphorylation/activation and necrosome formation, in the presence of ongoing caspase activation. Further, inhibition of TAK1 triggered two caspase 8 activation pathways through the induction of RIP1-FADD-caspase 8 complex as well as FLIP cleavage/degradation. Mechanistically, our data uncovered an essential role of the adaptor protein TRADD in caspase 8 activation and necrosome formation triggered by TAK1 inhibition. Moreover, ablation of the deubiqutinase CYLD prevented both apoptotic and necroptotic signaling induced by TAK1 inhibition, whereas deletion of the E3 ubiquitin ligase TRAF2 had the opposite effect. Finally, blocking the ubiquitin-proteasome pathway prevented the degradation of key necroptotic signaling proteins and necrosome formation. Thus we identified novel regulatory mechanisms underling the critical role of TAK1 in necroptotic signaling through regulation of multiple cell death checkpoints. Targeting key components of the necroptotic pathway (e.g., TRADD and CYLD) and the ubiquitin-proteasome pathway may represent novel therapeutic strategies for pathological conditions driven by necroptosis.

Participation of the ubiquitin-proteasome pathway in rat oocyte activation

Zygote ◽  
2005 ◽  
Vol 13 (1) ◽  
pp. 87-95 ◽  
Author(s):  
Xin Tan ◽  
An Peng ◽  
Yong-Chao Wang ◽  
Yue Wang ◽  
Qing-Yuan Sun
Keyword(s):  
Meiotic Division ◽  
Polar Body ◽  
Meiotic Spindle ◽  
Oocyte Activation ◽  
Parthenogenetic Activation ◽  
Ubiquitin Proteasome Pathway ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
Second Polar Body

The role of the ubiquitin-proteasome pathway (UPP) in mitosis is well known. However, its role in meiotic division is still poorly documented, especially in the activation of mammalian oocytes. In this study, the role of proteasome in the spontaneous and parthenogenetic activation of rat oocytes was investigated. We found that ALLN, an inhibitor of proteasome, when applied to metaphase II oocytes, inhibited spontaneous activation, blocked extrusion of the second polar body (PB) and caused the withdrawal of the partially extruded second PB. ALLN also inhibited the parthenogenetic activation induced by cycloheximide, but had no effect on the formation of pronuclei in activated eggs. In metaphase and anaphase, ubiquitin and proteasome localized to the meiotic spindle, concentrating on both sides of the oocyte–second PB boundary during PB extrusion. This pattern of cellular distribution suggests that UPP may have a role in regulating nuclear division and cytokinesis. Ubiquitin was seen to form a ring around the pronucleus, whereas proteasome was evenly distributed in the pronuclear region. Taken together, our results indicate that (1) UPP is required for the transitions of oocytes from metaphase II to anaphase II and from anaphase II to the end of meiosis; and (2) the UPP plays a role in cytokinesis of the second meiotic division.

scholarly journals The decreased SIRT1 level may account for the lipid profile in chronic kidney disease

2019 ◽  
Vol 26 (1) ◽  
Author(s):  
Gang Chen ◽  
Xuemei Li
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Lipid Profile ◽  
Regulatory Element ◽  
Low Density Lipoprotein ◽  
Lipid Synthesis ◽  
Density Lipoprotein ◽  
Premature Aging ◽  
Silent Information Regulator 1 ◽  
Sterol Regulatory Element

Abstract Dysregulated lipid profile with hypertriglyceridemia and increased low-density lipoprotein (LDL) is common in chronic kidney disease (CKD) whereas the reason is unclear. A similar phenomenon is found in the elder population. Silent information regulator-1 (SIRT1) associates with many modulators regulating lipid metabolism and results in increased expression of sterol regulatory element-binding proteins (SREBPs), which functions as a key modulator in lipid synthesis. Since CKD is being viewed as a premature aging model and SIRT1 is known to decrease during the process of aging, we hypothesize that SIRT1 level is reduced in the liver when CKD develops and eventually result in dysregulated lipid profile.

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