{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:45:50Z","timestamp":1774485950480,"version":"3.50.1"},"reference-count":51,"publisher":"The Company of Biologists","issue":"4","license":[{"start":{"date-parts":[[1994,4,1]],"date-time":"1994-04-01T00:00:00Z","timestamp":765158400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1994,4,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>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 \u03b1-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 &amp;gt;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.<\/jats:p>","DOI":"10.1242\/jcs.107.4.765","type":"journal-article","created":{"date-parts":[[2021,4,24]],"date-time":"2021-04-24T02:29:59Z","timestamp":1619231399000},"page":"765-774","source":"Crossref","is-referenced-by-count":53,"title":["Mutations in the non-helical linker segment L1-2 of keratin 5 in patients with Weber-Cockayne epidermolysis bullosa simplex"],"prefix":"10.1242","volume":"107","author":[{"given":"Yiu-mo","family":"Chan","sequence":"first","affiliation":[{"name":"1 Department of Molecular Genetics and Cell Biology, Howard Hughes Medical Institute, The University of Chicago, 5841 S. Maryland Avenue, Room N314, Chicago, IL 60637, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian-Chun","family":"Yu","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Genetics and Cell Biology, Howard Hughes Medical Institute, The University of Chicago, 5841 S. Maryland Avenue, Room N314, Chicago, IL 60637, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janine","family":"LeBlanc-Straceski","sequence":"additional","affiliation":[{"name":"3 Department of Molecular Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Christiano","sequence":"additional","affiliation":[{"name":"2 Departments of Dermatology and Biochemistry and Molecular Biology, Jefferson Medical College, Philadelphia, PA 19107, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leena","family":"Pulkkinen","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Genetics and Cell Biology, Howard Hughes Medical Institute, The University of Chicago, 5841 S. Maryland Avenue, Room N314, Chicago, IL 60637, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raju S.","family":"Kucherlapati","sequence":"additional","affiliation":[{"name":"3 Department of Molecular Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jouni","family":"Uitto","sequence":"additional","affiliation":[{"name":"2 Departments of Dermatology and Biochemistry and Molecular Biology, Jefferson Medical College, Philadelphia, PA 19107, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elaine","family":"Fuchs","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Genetics and Cell Biology, Howard Hughes Medical Institute, The University of Chicago, 5841 S. Maryland Avenue, Room N314, Chicago, IL 60637, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[1994,4,1]]},"reference":[{"key":"2024022707100087300_JOCES_107_4_765C1","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1083\/jcb.105.2.791","article-title":"The expression of mutant epidermal keratin cDNAs transfected in simple epithelial and squamous cell carcinoma lines","volume":"105","author":"Albers","year":"1987","journal-title":"J. Cell Biol"},{"key":"2024022707100087300_JOCES_107_4_765C2","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1083\/jcb.108.4.1477","article-title":"Expression of mutant keratin cDNAs in epithelial cells reveals possible mechanisms for initiation and assembly of intermediate filaments","volume":"108","author":"Albers","year":"1989","journal-title":"J. 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Cell Biol"}],"container-title":["Journal of Cell Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.biologists.com\/jcs\/article-pdf\/107\/4\/765\/3376240\/joces_107_4_765.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/jcs\/article-pdf\/107\/4\/765\/3376240\/joces_107_4_765.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T07:10:29Z","timestamp":1709017829000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/jcs\/article\/107\/4\/765\/24092\/Mutations-in-the-non-helical-linker-segment-L1-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,4,1]]},"references-count":51,"journal-issue":{"issue":"4","published-print":{"date-parts":[[1994,4,1]]}},"URL":"https:\/\/doi.org\/10.1242\/jcs.107.4.765","relation":{},"ISSN":["0021-9533","1477-9137"],"issn-type":[{"value":"0021-9533","type":"print"},{"value":"1477-9137","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,4,1]]}}}