ABSTRACT
Aberrant proteins located in the endoplasmic reticulum (ER) undergo rapid ubiquitination by multiple ubiquitin (Ub) E3 ligases and are retrotranslocated to the cytosol as part of the ER-associated degradation (ERAD). Despite several ERAD branches involving different Ub E3 ligases, the molecular machinery responsible for these ERAD branches in mammalian cells remains not fully understood. Through a series of multiplex knockdown/knockout experiments with real-time kinetic measurements, we demonstrate that HERC3 operates independently of the ER-embedded ubiquitin ligases RNF5 and RNF185 (RNF5/185) to mediate the retrotranslocation and ERAD of misfolded CFTR. While RNF5/185 participates in the ERAD process of both misfolded ABCB1 and CFTR, HERC3 uniquely promotes CFTR ERAD. In vitro assay revealed that HERC3 directly interacts with the exposed membrane-spanning domains (MSDs) of CFTR but not with the MSDs embedded in liposomes. Therefore, HERC3 could play a role in the quality control of MSDs in the cytoplasm and might be crucial for the ERAD pathway of select membrane proteins.
Subject(s)
Endoplasmic Reticulum-Associated Degradation , Membrane Proteins , Ubiquitin-Protein Ligases , Humans , Cystic Fibrosis Transmembrane Conductance Regulator/metabolism , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , DNA-Binding Proteins , Endoplasmic Reticulum/metabolism , Guanine Nucleotide Exchange Factors/metabolism , Guanine Nucleotide Exchange Factors/genetics , HEK293 Cells , HeLa Cells , Membrane Proteins/chemistry , Membrane Proteins/metabolism , Protein Binding , Protein Domains , Protein Folding , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics , UbiquitinationABSTRACT
Prevotella bivia (P. bivia) is an anaerobic Gram-negative rod usually inhabiting in the urogenital system, and sometimes in the intra-oral space, whose infection to other parts of body is extremely rare. In this report, we describe a rare case of a recurrent infectious abscess due to P. bivia in the right shoulder of a middle-aged female.
Subject(s)
Bacteroidaceae Infections , Abscess/complications , Abscess/diagnosis , Abscess/drug therapy , Bacteroidaceae Infections/diagnosis , Female , Humans , Middle Aged , PrevotellaSubject(s)
Bone Diseases/diagnosis , Cervical Vertebrae/microbiology , Mycobacterium avium-intracellulare Infection/diagnosis , Sternum/microbiology , Aged, 80 and over , Bone Diseases/microbiology , Bone Diseases/pathology , Cervical Vertebrae/pathology , Female , Humans , Mycobacterium avium Complex , Mycobacterium avium-intracellulare Infection/pathology , Sternum/pathologyABSTRACT
A 41-year-old man visited our dermatology clinic because an eruption, which was resistant to steroid ointment treatment, had appeared on his right forearm. An oval, soybean-sized erythematous infiltrated lesion with scales and crusts was located in the central part of the extensor surface of the right forearm and showed partial erosion with attached yellow crusts. The lesion had an impetigo-like appearance. Fungal elements were confirmed from the scales by KOH examination and the fungus was identified as Trichophyton tonsurans by fungal culture and molecular method. Clinical features of T. tonsurans infection vary, wherein some patients have strong inflammatory manifestations, while others remain as asymptomatic carriers. Especially at the early stage of the infection, diagnosis is difficult because it is often misdiagnosed as eczema. We report a case of T. tonsurans infection that had impetigo-like appearance. We also studied the mechanism of the disease.
