TY - JOUR
T1 - Defining keratin protein function in skin epithelia
T2 - Epidermolysis bullosa simplex and its aftermath
AU - Coulombe, Pierre A.
AU - Lee, Chang Hun
N1 - Funding Information:
We thank members of the laboratory for support and Dr Bernard Cohen for providing an illustration. Relevant efforts in the laboratory are supported by grants AR42047, AR44232, and CA160255 from the National Institutes of Health.
PY - 2012/3
Y1 - 2012/3
N2 - Epidermolysis bullosa simplex (EBS) is a rare genetic condition typified by superficial bullous lesions following incident frictional trauma to the skin. Most cases of EBS are due to dominantly acting mutations in keratin 14 (K14) or K5, the type I and II intermediate filament (IF) proteins that copolymerize to form a pancytoplasmic network of 10 nm filaments in basal keratinocytes of epidermis and related epithelia. Defects in K5-K14 filament network architecture cause basal keratinocytes to become fragile, and account for their rupture upon exposure to mechanical trauma. The discovery of the etiology and pathophysiology of EBS was intimately linked to the quest for an understanding of the properties and function of keratin filaments in skin epithelia. Since then, continued cross-fertilization between basic science efforts and clinical endeavors has highlighted several additional functional roles for keratin proteins in the skin, suggested new avenues for effective therapies for keratin-based diseases, and expanded our understanding of the remarkable properties of the skin as an organ system.
AB - Epidermolysis bullosa simplex (EBS) is a rare genetic condition typified by superficial bullous lesions following incident frictional trauma to the skin. Most cases of EBS are due to dominantly acting mutations in keratin 14 (K14) or K5, the type I and II intermediate filament (IF) proteins that copolymerize to form a pancytoplasmic network of 10 nm filaments in basal keratinocytes of epidermis and related epithelia. Defects in K5-K14 filament network architecture cause basal keratinocytes to become fragile, and account for their rupture upon exposure to mechanical trauma. The discovery of the etiology and pathophysiology of EBS was intimately linked to the quest for an understanding of the properties and function of keratin filaments in skin epithelia. Since then, continued cross-fertilization between basic science efforts and clinical endeavors has highlighted several additional functional roles for keratin proteins in the skin, suggested new avenues for effective therapies for keratin-based diseases, and expanded our understanding of the remarkable properties of the skin as an organ system.
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U2 - 10.1038/jid.2011.450
DO - 10.1038/jid.2011.450
M3 - Review article
C2 - 22277943
AN - SCOPUS:84862776648
SN - 0022-202X
VL - 132
SP - 763
EP - 775
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 3 PART 2
ER -