Novel and recurrent mutations in keratinKRT5andKRT14genes in epidermolysis bullosa simplex: implications for disease phenotype and keratin filament assembly

2006 ◽  
Vol 27 (7) ◽  
pp. 719-720 ◽  
Author(s):  
Felix B. Müller ◽  
Wolfgang Küster ◽  
Kerstin Wodecki ◽  
Hiram Almeida ◽  
Leena Bruckner-Tuderman ◽  
...  
Keyword(s):  
Epidermolysis Bullosa ◽  
Disease Phenotype ◽  
Epidermolysis Bullosa Simplex ◽  
Filament Assembly ◽  
Recurrent Mutations ◽  
Keratin Filament

Mutations in the non-helical linker segment L1-2 of keratin 5 in patients with Weber-Cockayne epidermolysis bullosa simplex

1994 ◽  
Vol 107 (4) ◽  
pp. 765-774
Author(s):  
Y.M. Chan ◽  
Q.C. Yu ◽  
J. LeBlanc-Straceski ◽  
A. Christiano ◽  
L. Pulkkinen ◽  
...  
Keyword(s):  
Epidermolysis Bullosa ◽  
Intermediate Filament ◽  
Point Mutations ◽  
Epidermolysis Bullosa Simplex ◽  
Keratin Gene ◽  
Filament Assembly ◽  
Keratin Polypeptides ◽  
Epidermolytic Hyperkeratosis ◽  
Hands And Feet ◽  
Linker Segment

Keratins are the major structural proteins of the epidermis. Analyzing keratin gene sequences, appreciating the switch in keratin gene expression that takes place as epidermal cells commit to terminally differentiate, and elucidating how keratins assemble into 10 nm filaments, have provided the foundation that has led to the discoveries of the genetic bases of two major classes of human skin diseases, epidermolysis bullosa simplex (EBS) and epidermolytic hyperkeratosis (EH). These diseases involve point mutations in either the basal epidermal keratin pair, K5 and K14 (EBS), or the suprabasal pair, K1 and K10 (EH). In severe cases of EBS and EH, mutations are found in the highly conserved ends of the alpha-helical rod domain, regions that, by random mutagenesis, had already been found to be important for 10 nm filament assembly. In order to identify regions of the keratin polypeptides that might be more subtly involved in 10 nm filament assembly and to explore the diversity in mutations within milder cases of these diseases, we have focused on Weber-Cockayne EBS, where mild blistering occurs primarily on the hands and feet in response to mechanical stress. In this report, we show that affected members of two different W-C EBS families have point mutations within 1 residue of each other in the non-helical linker segment of the K5 polypeptide. Genetic linkage analyses, the absence of this mutation in > 150 wild-type alleles and filament assembly studies suggest that these mutations are responsible for the W-C EBS phenotype. These findings provide the best evidence to date that the non-helical linker region in the middle of the keratin polypeptides plays a subtle but significant role in intermediate filament structure and/or intermediate filament cytoskeletal architecture.

scholarly journals Threonine 150 Phosphorylation of Keratin 5 Is Linked to Epidermolysis Bullosa Simplex and Regulates Filament Assembly and Cell Viability

2018 ◽  
Vol 138 (3) ◽  
pp. 627-636 ◽  
Author(s):  
Mugdha Sawant ◽  
Nicole Schwarz ◽  
Reinhard Windoffer ◽  
Thomas M. Magin ◽  
Jan Krieger ◽  
...  
Keyword(s):  
Cell Viability ◽  
Epidermolysis Bullosa ◽  
Epidermolysis Bullosa Simplex ◽  
Keratin 5 ◽  
Filament Assembly

Novel and recurrent mutations in Keratin 5 and 14 in Korean patients with Epidermolysis bullosa simplex

2010 ◽  
Vol 57 (2) ◽  
pp. 90-94 ◽  
Author(s):  
Tae-Won Kang ◽  
Jeong Seon Lee ◽  
Song-Ee Kim ◽  
Se-Woong Oh ◽  
Soo-Chan Kim
Keyword(s):  
Epidermolysis Bullosa ◽  
Epidermolysis Bullosa Simplex ◽  
Korean Patients ◽  
Keratin 5 ◽  
Recurrent Mutations

scholarly journals Damaged Keratin Filament Network Caused by KRT5 Mutations in Localized Recessive Epidermolysis Bullosa Simplex

2021 ◽  
Vol 12 ◽  
Author(s):  
Fuying Chen ◽  
Lei Yao ◽  
Xue Zhang ◽  
Yan Gu ◽  
Hong Yu ◽  
...  
Keyword(s):  
Epidermolysis Bullosa ◽  
Mapk Signaling ◽  
Epidermolysis Bullosa Simplex ◽  
Protein Levels ◽  
Keratin 5 ◽  
Keratin Filament ◽  
Filament Network ◽  
Keratin Intermediate Filaments ◽  
Desmosomal Protein

Epidermolysis bullosa simplex (EBS) is a blistering dermatosis that is mostly caused by dominant mutations in KRT5 and KRT14. In this study, we investigated one patient with localized recessive EBS caused by novel homozygous c.1474T > C mutations in KRT5. Biochemical experiments showed a mutation-induced alteration in the keratin 5 structure, intraepidermal blisters, and collapsed keratin intermediate filaments, but no quantitative change at the protein levels and interaction between keratin 5 and keratin 14. Moreover, we found that MAPK signaling was inhibited, while desmosomal protein desmoglein 1 (DSG1) was upregulated upon KRT5 mutation. Inhibition of EGFR phosphorylation upregulated DSG1 levels in an in vitro model. Collectively, our findings suggest that this mutation leads to localized recessive EBS and that keratin 5 is involved in maintaining DSG1 via activating MAPK signaling.

Sign in / Sign up

Export Citation Format

Share Document