scholarly journals AIRE Functions As an E3 Ubiquitin Ligase

2004 ◽  
Vol 199 (2) ◽  
pp. 167-172 ◽  
Author(s):  
Daisuke Uchida ◽  
Shigetsugu Hatakeyama ◽  
Akemi Matsushima ◽  
Hongwei Han ◽  
Satoshi Ishido ◽  
...  
Keyword(s):  
E3 Ligase ◽  
Autosomal Recessive Inheritance ◽  
Missense Mutations ◽  
The Novel ◽  
Aire Gene ◽  
Enzymatic Function ◽  
Self Tolerance ◽  
Organ Specific ◽  
Proteasome Pathway

Autoimmune regulator (AIRE) gene mutation is responsible for the development of autoimmune-polyendocrinopathy-candidiasis ectodermal dystrophy, an organ-specific autoimmune disease with monogenic autosomal recessive inheritance. AIRE is predominantly expressed in medullary epithelial cells of the thymus and is considered to play important roles in the establishment of self-tolerance. AIRE contains two plant homeodomain (PHD) domains, and the novel role of PHD as an E3 ubiquitin (Ub) ligase has just emerged. Here we show that the first PHD (PHD1) of AIRE mediates E3 ligase activity. The significance of this finding was underscored by the fact that disease-causing missense mutations in the PHD1 (C311Y and P326Q) abolished its E3 ligase activity. These results add a novel enzymatic function for AIRE and suggest an indispensable role of the Ub proteasome pathway in the establishment of self-tolerance, in which AIRE is involved.

scholarly journals Erbin is a novel substrate of the Sag-βTrCP E3 ligase that regulates KrasG12D-induced skin tumorigenesis

2015 ◽  
Vol 209 (5) ◽  
pp. 721-738 ◽  
Author(s):  
Chuan-Ming Xie ◽  
Dongping Wei ◽  
Lili Zhao ◽  
Sylvie Marchetto ◽  
Lin Mei ◽  
...  
Keyword(s):  
Mammalian Target Of Rapamycin ◽  
E3 Ligase ◽  
Ros Generation ◽  
Targeted Deletion ◽  
Ras Activation ◽  
Specific Tumor ◽  
Ros Accumulation ◽  
Organ Specific ◽  
New Gene

SAG/RBX2 is the RING (really interesting new gene) component of Cullin-RING ligase, which is required for its activity. An organ-specific role of SAG in tumorigenesis is unknown. We recently showed that Sag/Rbx2, upon lung-targeted deletion, suppressed KrasG12D-induced tumorigenesis via inactivating NF-κB and mammalian target of rapamycin pathways. In contrast, we report here that, upon skin-targeted deletion, Sag significantly accelerated KrasG12D-induced papillomagenesis. In KrasG12D-expressing primary keratinocytes, Sag deletion promotes proliferation by inhibiting autophagy and senescence, by inactivating the Ras–Erk pathway, and by blocking reactive oxygen species (ROS) generation. This is achieved by accumulation of Erbin to block Ras activation of Raf and Nrf2 to scavenge ROS and can be rescued by knockdown of Nrf2 or Erbin. Simultaneous one-allele deletion of the Erbin-encoding gene Erbb2ip partially rescued the phenotypes. Finally, we characterized Erbin as a novel substrate of SAG-βTrCP E3 ligase. By degrading Erbin and Nrf2, Sag activates the Ras–Raf pathway and causes ROS accumulation to trigger autophagy and senescence, eventually delaying KrasG12D-induced papillomagenesis and thus acting as a skin-specific tumor suppressor.

scholarly journals Clinical case report: history of diagnosis and clinical features of type autoimmune polyglandular syndrome 1

2019 ◽  
Vol 65 (5) ◽  
pp. 362-366
Author(s):  
Viktoriya V. Troshina ◽  
Natalia Yu. Romanova ◽  
Leila S. Sozaeva ◽  
Ekaterina A. Troshina
Keyword(s):  
Case Report ◽  
Autosomal Recessive Inheritance ◽  
Risk Groups ◽  
Clinical Criteria ◽  
Autoimmune Polyglandular Syndrome ◽  
Aire Gene ◽  
Organ Specific ◽  
History Of ◽  
Autoimmune Polyglandular Syndrome Type

Autoimmune polyglandular syndrome type 1 (APS-1) is a rare disease with autosomal recessive inheritance and it caused by mutations in the autoimmune regulator (AIRE) gene. This disease has clinical polymorphism that including besides endocrinopathies other organ-specific manifestations and that complicates to diagnose of this condition on time. However, most often APS-1 has a characteristic debut and a certain stage of clinical symptom manifestation. This article describes a case report of an 18-year-old patient with confirmed APS-1, in which the course of disease was erased over a long period of life and didnt meet of clinical criteria for the diagnosis in this syndrome. A high quality of life for such patients is possible with timely, individually selected replacement therapy with subsequent follow-up. It is important to remember the need for screening in risk groups for the formation of clinical forms of APS among the subjects presenting with a single endocrine pathology. The continuity of medical supervision by pediatric and adult endocrinological service physicians must be respected that can be traced on the example of the case from our practice.

scholarly journals Noncanonical role of Arabidopsis COP1/SPA complex in repressing BIN2-mediated PIF3 phosphorylation and degradation in darkness

2017 ◽  
Vol 114 (13) ◽  
pp. 3539-3544 ◽  
Author(s):  
Jun-Jie Ling ◽  
Jian Li ◽  
Danmeng Zhu ◽  
Xing Wang Deng
Keyword(s):  
E3 Ligase ◽  
26S Proteasome ◽  
Complex Action ◽  
Precise Control ◽  
Strong Stabilization ◽  
Proteasome Pathway

The E3 ligase CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1) has been known to mediate key signaling factors for degradation via the ubiquitin/26S proteasome pathway in both plants and animals. Here, we report a noncanonical function of Arabidopsis COP1, the central repressor of photomorphogenesis, in the form of a COP1/ SUPPRESSOR of phyA-105 (SPA) complex. We show that the COP1/SPA complex associates with and stabilizes PHYTOCHROME INTERACTING FACTOR 3 (PIF3) to repress photomorphogenesis in the dark. We identify the GSK3-like kinase BRASSINOSTEROID-INSENSITIVE 2 (BIN2) as a kinase of PIF3, which induces PIF3 degradation via 26S proteasome during skotomorphogenesis. Mutations on two typical BIN2 phosphorylation motifs of PIF3 lead to a strong stabilization of the protein in the dark. We further show that the COP1/SPA complex promotes PIF3 stability by repressing BIN2 activity. Intriguingly, without affecting BIN2 expression, the COP1/SPA complex modulates BIN2 activity through interfering with BIN2–PIF3 interaction, thereby inhibiting BIN2-mediated PIF3 phosphorylation and degradation. Taken together, our results suggest another paradigm for COP1/SPA complex action in the precise control of skotomorphogenesis.

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.

ROLE OF THE NOVEL INTRODUCED PAN-INTESTINAL CAPSULE ENDOSCOPY SYSTEM IN CELIAC DISEASE

2019 ◽  
Author(s):  
F Foerster ◽  
K Mönkemüller ◽  
PR Galle ◽  
H Neumann
Keyword(s):  
Celiac Disease ◽  
Capsule Endoscopy ◽  
The Novel

Anti-Myelin Oligodendrocyte Glycoprotein Encephalomyelitis and Extensive Longitudinal Transverse Myelitis Associated with Compound Heterozygous NLRP3 Missense Mutations in a Young Child

2020 ◽  
Author(s):  
Deirdre O'Sullivan ◽  
Michael Moore ◽  
Susan Byrne ◽  
Andreas O. Reiff ◽  
Susanna Felsenstein
Keyword(s):  
Young Child ◽  
Genetic Basis ◽  
Transverse Myelitis ◽  
Acute Disseminated Encephalomyelitis ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Compound Heterozygous ◽  
Missense Mutations ◽  
Childhood Onset

AbstractAcute disseminated encephalomyelitis in association with extensive longitudinal transverse myelitis is reported in a young child with positive anti-myelin oligodendrocyte glycoprotein (MOG) antibody with heterozygous NLRP3 missense mutations; p.(Arg488Lys) and p.(Ser159Ile). This case may well present an exceptional coincidence, but may describe a yet unrecognized feature of the spectrum of childhood onset cryopyrinopathies that contribute to the understanding of the genetic basis for anti-MOG antibody positive encephalomyelitis. Based on this observation, a larger scale study investigating the role of NLRP3 and other inflammasomes in this entity would provide important pathophysiological insights and potentially novel avenues for treatment.

Patterns: Rosamond Lehmann

2018 ◽  
Author(s):  
Vike Martina Plock
Keyword(s):  
Coming Of Age ◽  
Public Image ◽  
Market Forces ◽  
The Novel ◽  
Fashion Industry ◽  
To The Lighthouse ◽  
Fashion Magazines ◽  
Female Authorship ◽  
Rosamond Lehmann

This chapter analyzes the role of fashion as a discursive force in Rosamond Lehmann’s 1932 coming-of-age novel Invitation to the Waltz. Reading the novel alongside such fashion magazines as Vogue, it demonstrates Lehmann’s awareness that 1920s fashion, in spite of its carefully stylized public image as harbinger of originality, emphasized the importance of following preconceived (dress) patterns in the successful construction of modern feminine types. Invitation to the Waltz, it argues, opposes the production of patterned types and celebrates difference and disobedience in its stead. At the same time, the novel’s formal appearance is nonetheless dependent on the very same tenets it criticizes. On closer scrutiny, it is seen to reveal its resemblance to Virginia Woolf’s To the Lighthouse (1927). A tension between imitation and originality determines sartorial fashion choices. This chapter shows that female authorship in the inter-war period was subjected to the same market forces that controlled and sustained the organization of the fashion industry.

SARS-COV2 virus and Coronavirus disease (COVID-19)

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 977-982
Author(s):  
Mohamed J. Saadh ◽  
Bashar Haj Rashid M ◽  
Roa’a Matar ◽  
Sajeda Riyad Aldibs ◽  
Hala Sbaih ◽  
...  
Keyword(s):  
Close Contact ◽  
Antiviral Agents ◽  
Health Concern ◽  
The Novel ◽  
Global Public Health ◽  
Fatal Disease ◽  
Mild Disease ◽  
Life Threatening ◽  
Novel Coronavirus

SARS-COV2 virus causes Coronavirus disease (COVID-19) and represents the causative agent of a potentially fatal disease that is of great global public health concern. The novel coronavirus (2019) was discovered in 2019 in Wuhan, the market of the wet animal, China with viral pneumonia cases and is life-threatening. Today, WHO announces COVID-19 outbreak as a pandemic. COVID-19 is likely to be zoonotic. It is transmitted from bats as intermediary animals to human. Also, the virus is transmitted from human to human who is in close contact with others. The computerized tomographic chest scan is usually abnormal even in those with no symptoms or mild disease. Treatment is nearly supportive; the role of antiviral agents is yet to be established. The SARS-COV2 virus spreads faster than its two ancestors, the SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), but has lower fatality. In this article, we aimed to summarize the transmission, symptoms, pathogenesis, diagnosis, treatment, and vaccine to control the spread of this fatal disease.

THE ROLE OF ARTISTIC PSYCHOLOGY IN THE METAPHORICAL HARMONY OF MAN AND THE REALITY OF LIFE

2020 ◽  
Vol 2 (3) ◽  
pp. 19-23
Author(s):  
Shakhlo Botirova ◽  
Keyword(s):  
The Novel

In this article , in the novel “Rebellion and obedience” by Ulugbek Hamdam, the author analyzes the artistic psychological description of a person on the path of development in the center of an integral complex metaphorical system of being. The novel “Rebellion and obedience” is based onthe method of metaphorization of reality. In it, a personexperiences vertigo about who he is and what powerful being he possesses. The reason for this is a riot. After much agony, he obeys. Allegedly thus proves its existence. Finds answers to certain riddles

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