Genomes and Genes
Gene Symbol: Krt6
Description: keratin 6
Alias: Krt-2.6, Krt2-6, keratin complex 2, basic, gene 6
- Jiang C, Magnaldo T, Ohtsuki M, Freedberg I, Bernerd F, Blumenberg M. Epidermal growth factor and transforming growth factor alpha specifically induce the activation- and hyperproliferation-associated keratins 6 and 16. Proc Natl Acad Sci U S A. 1993;90:6786-90 pubmed..Thus, EGF specifically induces K6 and K16, markers of activated keratinocytes, via nuclear proteins that bind to EGF-responsive elements in the promoters of these keratin genes. ..
- Shimizu Y, Thumkeo D, Keel J, Ishizaki T, Oshima H, Oshima M, et al. ROCK-I regulates closure of the eyelids and ventral body wall by inducing assembly of actomyosin bundles. J Cell Biol. 2005;168:941-53 pubmed..These results suggest that ROCK-I regulates closure of the eyelids and ventral body wall through organization of actomyosin bundles. ..
- Kaufman C, Zhou P, Pasolli H, Rendl M, Bolotin D, Lim K, et al. GATA-3: an unexpected regulator of cell lineage determination in skin. Genes Dev. 2003;17:2108-22 pubmed..This newfound function for GATA-3 in skin development strengthens the parallels between the differentiation programs governing hair follicle and lymphocyte differentiation. ..
- Foley J, Dann P, Hong J, Cosgrove J, Dreyer B, Rimm D, et al. Parathyroid hormone-related protein maintains mammary epithelial fate and triggers nipple skin differentiation during embryonic breast development. Development. 2001;128:513-25 pubmed..Finally, PTHrP signaling regulates the epidermal and mesenchymal expression of LEF1 and (&bgr;)-catenin, suggesting that these changes in cell fate involve an interaction between the PTHrP and Wnt signaling pathways. ..
- Mazzalupo S, Coulombe P. A reporter transgene based on a human keratin 6 gene promoter is specifically expressed in the periderm of mouse embryos. Mech Dev. 2001;100:65-9 pubmed..A subset of periderm cells, localized to temporary epithelial fusions, is known to contain keratin 6 protein, and we find that these cells also harbor LacZ enzymatic activity. ..
- McGowan K, Coulombe P. Onset of keratin 17 expression coincides with the definition of major epithelial lineages during skin development. J Cell Biol. 1998;143:469-86 pubmed..The pattern of K17 gene expression during development has direct implications for the morphogenesis of skin epithelia, and points to the existence of a molecular relationship between development and wound repair. ..
- Cottle D, Ursino G, Ip S, Jones L, DiTommaso T, Hacking D, et al. Fetal inhibition of inflammation improves disease phenotypes in harlequin ichthyosis. Hum Mol Genet. 2015;24:436-49 pubmed publisher..These studies highlight inflammation as an unexpected contributor to HI disease development in utero, and suggest that inhibiting inflammation may reduce disease severity. ..
- Ray S, Foote H, Lechler T. beta-Catenin protects the epidermis from mechanical stresses. J Cell Biol. 2013;202:45-52 pubmed publisher..These data demonstrate that a complete understanding of the functions of cell adhesion proteins must take into account their roles in response to mechanical stresses. ..
- Martinez P, Ferrara Romeo I, Flores J, Blasco M. Essential role for the TRF2 telomere protein in adult skin homeostasis. Aging Cell. 2014;13:656-68 pubmed publisher..These results are in contrast with conditional deletion of TRF1 and TPP1 in the skin, where p53 deficiency rescued the associated skin phenotypes, highlighting the comparatively more essential role of TRF2 in skin homeostasis. ..
- Blanco S, Kurowski A, Nichols J, Watt F, Benitah S, Frye M. The RNA-methyltransferase Misu (NSun2) poises epidermal stem cells to differentiate. PLoS Genet. 2011;7:e1002403 pubmed publisher..Our results reveal that post-transcriptional RNA methylation can play a previously unappreciated role in controlling stem cell fate. ..
- Ruiz S, Segrelles C, Bravo A, Santos M, Perez P, Leis H, et al. Abnormal epidermal differentiation and impaired epithelial-mesenchymal tissue interactions in mice lacking the retinoblastoma relatives p107 and p130. Development. 2003;130:2341-53 pubmed..These results indicate an essential role for p107 and p130 in the epithelial-mesenchimal interactions. ..
- Wakabayashi N, Itoh K, Wakabayashi J, Motohashi H, Noda S, Takahashi S, et al. Keap1-null mutation leads to postnatal lethality due to constitutive Nrf2 activation. Nat Genet. 2003;35:238-45 pubmed..Breeding to Nrf2-deficient mice reversed the phenotypic Keap1 deficiencies. These experiments show that Keap1 acts upstream of Nrf2 in the cellular response to oxidative and xenobiotic stress. ..
- Takabayashi S, Katoh H. A mutant mouse with severe anemia and skin abnormalities controlled by a new allele of the flaky skin (fsn) locus. Exp Anim. 2005;54:339-47 pubmed..5 dpc to 18.5 dpc). Time differences in the appearance of the different phenotypes observed in various tissue and organs of fsn homozygotes suggest they are caused by expression of the fsn gene at different developmental stages. ..
- El Shahawy M, Reibring C, Neben C, Hallberg K, Marangoni P, Harfe B, et al. Cell fate specification in the lingual epithelium is controlled by antagonistic activities of Sonic hedgehog and retinoic acid. PLoS Genet. 2017;13:e1006914 pubmed publisher..These findings reveal key functions for SHH and RA in cell fate specification in the lingual epithelium and aid in deciphering the molecular mechanisms that assign cell identity. ..
- Curtain M, Heffner C, Maddox D, Gudis P, Donahue L, Murray S. A novel allele of Alx4 results in reduced Fgf10 expression and failure of eyelid fusion in mice. Mamm Genome. 2015;26:173-80 pubmed publisher..Together, these data demonstrate that eyelid fusion in mice requires the expression of Alx4, accompanied by the loss of normal expression of essential components of the eyelid fusion pathway. ..
- Mlitz V, Strasser B, Jaeger K, Hermann M, Ghannadan M, Buchberger M, et al. Trichohyalin-like proteins have evolutionarily conserved roles in the morphogenesis of skin appendages. J Invest Dermatol. 2014;134:2685-2692 pubmed publisher..The results of this study show that SFTP-positive epithelia function as scaffolds for the growth of diverse skin appendages such as claws, nails, hair, and feathers, indicating a common evolutionary origin. ..
- Wang X, Ouyang H, Yamamoto Y, Kumar P, Wei T, Dagher R, et al. Residual embryonic cells as precursors of a Barrett's-like metaplasia. Cell. 2011;145:1023-35 pubmed publisher..Our findings suggest that certain precancerous lesions, such as Barrett's, initiate not from genetic alterations but from competitive interactions between cell lineages driven by opportunity...
- Danussi C, Petrucco A, Wassermann B, Pivetta E, Modica T, Del Bel Belluz L, et al. EMILIN1-?4/?9 integrin interaction inhibits dermal fibroblast and keratinocyte proliferation. J Cell Biol. 2011;195:131-45 pubmed publisher..In addition, EMILIN1 is identified as a novel ligand for keratinocyte ?9?1 integrin, suggesting prospective roles for this receptor-ligand pair in skin homeostasis. ..
- Ganuza M, Saiz Ladera C, Canamero M, Gomez G, Schneider R, Blasco M, et al. Genetic inactivation of Cdk7 leads to cell cycle arrest and induces premature aging due to adult stem cell exhaustion. EMBO J. 2012;31:2498-510 pubmed publisher..This process, a physiological attempt to maintain tissue homeostasis, led to the attrition of adult stem cell pools and to the appearance of age-related phenotypes, including telomere shortening and early death. ..
- Chen L, Yang Yen H, Tsai C, Thio C, Chuang H, Yang L, et al. Protein Palmitoylation by ZDHHC13 Protects Skin against Microbial-Driven Dermatitis. J Invest Dermatol. 2017;137:894-904 pubmed publisher..In summary, our study suggests that loss of ZDHHC13 in skin impairs the integrity of multiple barrier functions and leads to a dermatitis lesion in response to microbial encounters. ..
- Finch J, Andrews K, Krieg P, Furstenberger G, Slaga T, Ootsuyama A, et al. Identification of a cloned sequence activated during multi-stage carcinogenesis in mouse skin. Carcinogenesis. 1991;12:1519-22 pubmed..The overexpression of the mal2 or keratin K6 gene in malignant SCCs was independent of the protocol, either chemical or radiation, that was used to induce the tumors. ..
- Li C, Guo H, Xu X, Weinberg W, Deng C. Fibroblast growth factor receptor 2 (Fgfr2) plays an important role in eyelid and skin formation and patterning. Dev Dyn. 2001;222:471-83 pubmed..Notably, mutant skin remains thin with decreased hair density after transplantation to wild-type recipients. These data demonstrate an essential role of Fgfr2 in eyelid and skin formation and patterning. ..
- Murray S, Oram K, Gridley T. Multiple functions of Snail family genes during palate development in mice. Development. 2007;134:1789-97 pubmed
- Mailleux A, Overholtzer M, Schmelzle T, Bouillet P, Strasser A, Brugge J. BIM regulates apoptosis during mammary ductal morphogenesis, and its absence reveals alternative cell death mechanisms. Dev Cell. 2007;12:221-34 pubmed..These data provide important mechanistic information on the processes involved in sculpting the mammary gland and demonstrate that BIM is a critical regulator of apoptosis in vivo. ..
- Rothnagel J, Seki T, Ogo M, Longley M, Wojcik S, Bundman D, et al. The mouse keratin 6 isoforms are differentially expressed in the hair follicle, footpad, tongue and activated epidermis. Differentiation. 1999;65:119-30 pubmed..These studies suggest that the K6 isoforms have overlapping yet distinct expression profiles. ..
- Sevilla L, Latorre V, Sanchis A, Perez P. Epidermal inactivation of the glucocorticoid receptor triggers skin barrier defects and cutaneous inflammation. J Invest Dermatol. 2013;133:361-70 pubmed publisher..Together, our results show that epidermal loss of GR provokes skin barrier defects and cutaneous inflammation...
- Nakamura M, Matzuk M, Gerstmayer B, Bosio A, Lauster R, Miyachi Y, et al. Control of pelage hair follicle development and cycling by complex interactions between follistatin and activin. FASEB J. 2003;17:497-9 pubmed..These observations suggest that follistatin and activin interaction plays an important role in both HF development and cycling, possibly in part by regulating expression of BMP-2 and its antagonist. ..
- Peyrard Janvid M, Leslie E, Kousa Y, Smith T, Dunnwald M, Magnusson M, et al. Dominant mutations in GRHL3 cause Van der Woude Syndrome and disrupt oral periderm development. Am J Hum Genet. 2014;94:23-32 pubmed publisher..They supported the hypotheses that both genes are essential for the presence of a functional oral periderm and that failure of this process contributes to VWS. ..
- Seldin L, Muroyama A, Lechler T. NuMA-microtubule interactions are critical for spindle orientation and the morphogenesis of diverse epidermal structures. elife. 2016;5: pubmed publisher..Our results reveal an additional and direct function of NuMA during mitotic spindle positioning, as well as a reiterative use of spindle orientation in the skin to build diverse structures. ..
- Vaziri Sani F, Kaartinen V, El Shahawy M, Linde A, Gritli Linde A. Developmental changes in cellular and extracellular structural macromolecules in the secondary palate and in the nasal cavity of the mouse. Eur J Oral Sci. 2010;118:221-36 pubmed publisher..The hitherto-unknown innervation pattern of the developing palate was revealed. These findings may be of value for unravelling the pathogenesis of palatal clefting. ..
- Heyden A, Lützow Holm C, Clausen O, Brandtzaeg P, Huitfeldt H. Expression of keratins K6 and K16 in regenerating mouse epidermis is less restricted by cell replication than the expression of K1 and K10. Epithelial Cell Biol. 1994;3:96-101 pubmed..Our results suggest that the expression of K6 and K16 is less restricted by cellular replication than the normally occurring K1 and K10 keratins. ..
- Folgueras A, Guo X, Pasolli H, Stokes N, Polak L, Zheng D, et al. Architectural niche organization by LHX2 is linked to hair follicle stem cell function. Cell Stem Cell. 2013;13:314-27 pubmed publisher..These findings suggest that niche organization underlies the requirement for LHX2 in hair follicle structure and function. ..
- Sano T, Kume T, Fujimura T, Kawada H, Higuchi K, Iwamura M, et al. Long-term alteration in the expression of keratins 6 and 16 in the epidermis of mice after chronic UVB exposure. Arch Dermatol Res. 2009;301:227-37 pubmed publisher..Those events could have relevance to the mechanism of photo-damage, such as fine wrinkles observed in chronically UV-exposed skin in addition to dermal photo-aging. ..
- Torchia E, Zhang L, Huebner A, Sen S, Roop D. Aurora kinase-A deficiency during skin development impairs cell division and stratification. J Invest Dermatol. 2013;133:78-86 pubmed publisher..Thus, the deletion of Aurora-A in the developing epidermis alters centrosome function of basal keratinocytes and markedly impairs their ability to divide and stratify. ..
- Boglev Y, Wilanowski T, Caddy J, Parekh V, Auden A, Darido C, et al. The unique and cooperative roles of the Grainy head-like transcription factors in epidermal development reflect unexpected target gene specificity. Dev Biol. 2011;349:512-22 pubmed publisher..Our findings define the mechanisms underpinning the unique and cooperative roles of the Grhl genes in epidermal development. ..
- Owens P, Bazzi H, Engelking E, Han G, Christiano A, Wang X. Smad4-dependent desmoglein-4 expression contributes to hair follicle integrity. Dev Biol. 2008;322:156-66 pubmed publisher..Thus, Smad4 loss-associated Dsg4 depletion contributed, at least in part, to hair follicles degeneration in Smad4 deficient skin. ..
- Darido C, Georgy S, Wilanowski T, Dworkin S, Auden A, Zhao Q, et al. Targeting of the tumor suppressor GRHL3 by a miR-21-dependent proto-oncogenic network results in PTEN loss and tumorigenesis. Cancer Cell. 2011;20:635-48 pubmed publisher..Our data define the GRHL3-PTEN axis as a critical tumor suppressor pathway in SCC. ..
- Taylor D, Bubier J, Silva K, Sundberg J. Development, structure, and keratin expression in C57BL/6J mouse eccrine glands. Vet Pathol. 2012;49:146-54 pubmed publisher..These data serve as a valuable reference for investigators who use genetically engineered mice for skin research. ..
- Kist R, Watson M, Crosier M, Robinson M, Fuchs J, Reichelt J, et al. The formation of endoderm-derived taste sensory organs requires a Pax9-dependent expansion of embryonic taste bud progenitor cells. PLoS Genet. 2014;10:e1004709 pubmed publisher..In this pathway, Pax9 is essential to generate a pool of taste bud progenitors and to maintain their competence towards prosensory cell fate induction. ..
- Dowling J, Yu Q, Fuchs E. Beta4 integrin is required for hemidesmosome formation, cell adhesion and cell survival. J Cell Biol. 1996;134:559-72 pubmed
- Magin T. Lessons from keratin transgenic and knockout mice. Subcell Biochem. 1998;31:141-72 pubmed
- Rountree R, Willis C, Dinh H, Blumberg H, Bailey K, Dean C, et al. RIP4 regulates epidermal differentiation and cutaneous inflammation. J Invest Dermatol. 2010;130:102-12 pubmed publisher..These data suggest that RIP4 functions in the epidermis through PKC-specific signaling pathways to regulate differentiation and inflammation. ..
- Ihrie R, Marques M, Nguyen B, Horner J, Papazoglu C, Bronson R, et al. Perp is a p63-regulated gene essential for epithelial integrity. Cell. 2005;120:843-56 pubmed..These findings demonstrate that Perp is a key effector in the p63 developmental program, playing an essential role in an adhesion subprogram central to epithelial integrity and homeostasis. ..
- Mazzalupo S, Wong P, Martin P, Coulombe P. Role for keratins 6 and 17 during wound closure in embryonic mouse skin. Dev Dyn. 2003;226:356-65 pubmed
- Richardson R, Hammond N, Coulombe P, Saloranta C, Nousiainen H, Salonen R, et al. Periderm prevents pathological epithelial adhesions during embryogenesis. J Clin Invest. 2014;124:3891-900 pubmed publisher..Furthermore, this study suggests that failure of periderm formation underlies a series of devastating birth defects, including popliteal pterygium syndrome, cocoon syndrome, and Bartsocas-Papas syndrome. ..
- Leslie E, Taub M, Liu H, Steinberg K, Koboldt D, Zhang Q, et al. Identification of functional variants for cleft lip with or without cleft palate in or near PAX7, FGFR2, and NOG by targeted sequencing of GWAS loci. Am J Hum Genet. 2015;96:397-411 pubmed publisher..This targeted sequencing study provides strong functional evidence implicating several specific variants as primary contributory risk alleles for nonsyndromic clefting in humans. ..
- Okano J, Lichti U, Mamiya S, Aronova M, Zhang G, Yuspa S, et al. Increased retinoic acid levels through ablation of Cyp26b1 determine the processes of embryonic skin barrier formation and peridermal development. J Cell Sci. 2012;125:1827-36 pubmed publisher..These results are important in understanding pathologies associated with abnormal embryonic skin development and barrier dysfunction. ..
- Sanchis A, Bayo P, Sevilla L, Perez P. Glucocorticoid receptor antagonizes EGFR function to regulate eyelid development. Int J Dev Biol. 2010;54:1473-80 pubmed publisher..5. Additionally, we demonstrate that GR regulates epithelial cell migration in vitro by interfering with EGFR-mediated signaling. Overall, GR/EGFR antagonism appears as a major mechanism regulating ocular epithelial development. ..
- Mill P, Lee A, Fukata Y, Tsutsumi R, Fukata M, Keighren M, et al. Palmitoylation regulates epidermal homeostasis and hair follicle differentiation. PLoS Genet. 2009;5:e1000748 pubmed publisher..This study is the first to demonstrate a key role for palmitoylation in regulating developmental signals in mammalian tissue homeostasis. ..
- Pichery M, Huchenq A, Sandhoff R, Severino Freire M, Zaafouri S, Opálka L, et al. PNPLA1 defects in patients with autosomal recessive congenital ichthyosis and KO mice sustain PNPLA1 irreplaceable function in epidermal omega-O-acylceramide synthesis and skin permeability barrier. Hum Mol Genet. 2017;26:1787-1800 pubmed publisher..Overall, our data support that PNPLA1/Pnpla1 is a key player in the formation of ?-O-acylceramide, a crucial process for the epidermal permeability barrier function. ..
- Yi R, O Carroll D, Pasolli H, Zhang Z, Dietrich F, Tarakhovsky A, et al. Morphogenesis in skin is governed by discrete sets of differentially expressed microRNAs. Nat Genet. 2006;38:356-62 pubmed..Here we characterize miRNAs in skin, the existence of which was hitherto unappreciated, and demonstrate their differential expression and importance in the morphogenesis of epithelial tissues within this vital organ. ..
- Rotty J, Coulombe P. A wound-induced keratin inhibits Src activity during keratinocyte migration and tissue repair. J Cell Biol. 2012;197:381-9 pubmed publisher..We conclude that K6 negatively regulates Src kinase activity and the migratory potential of skin keratinocytes during wound repair. Our findings may also be important in related contexts such as cancer. ..
- Michalik L, Desvergne B, Tan N, Basu Modak S, Escher P, Rieusset J, et al. Impaired skin wound healing in peroxisome proliferator-activated receptor (PPAR)alpha and PPARbeta mutant mice. J Cell Biol. 2001;154:799-814 pubmed..Thus, the findings presented here reveal unpredicted roles for PPARalpha and beta in adult mouse epidermal repair. ..
- Crish J, Conti M, Sakai T, Adelstein R, Egelhoff T. Keratin 5-Cre-driven excision of nonmuscle myosin IIA in early embryo trophectoderm leads to placenta defects and embryonic lethality. Dev Biol. 2013;382:136-48 pubmed publisher..5 in the forming epidermis, may be widely useful as drivers for activation of cre/lox based gene excision in early embryo extraembronic trophoblast tissues as well. ..
- Yamamoto T, Suzuki T, Kobayashi A, Wakabayashi J, Maher J, Motohashi H, et al. Physiological significance of reactive cysteine residues of Keap1 in determining Nrf2 activity. Mol Cell Biol. 2008;28:2758-70 pubmed publisher..These results demonstrate critical roles of the cysteine residues in vivo in maintaining Keap1 function, such that Nrf2 is repressed under quiescent conditions and active in response to oxidants/electrophiles. ..
- Kuraguchi M, Wang X, Bronson R, Rothenberg R, Ohene Baah N, Lund J, et al. Adenomatous polyposis coli (APC) is required for normal development of skin and thymus. PLoS Genet. 2006;2:e146 pubmed
- Byrd K, Lough K, Patel J, Descovich C, Curtis T, Williams S. LGN plays distinct roles in oral epithelial stratification, filiform papilla morphogenesis and hair follicle development. Development. 2016;143:2803-17 pubmed publisher..Thus, LGN has crucial tissue-specific functions in patterning surface ectoderm and its appendages by controlling division orientation. ..
- Takahashi K, Paladini R, Coulombe P. Cloning and characterization of multiple human genes and cDNAs encoding highly related type II keratin 6 isoforms. J Biol Chem. 1995;270:18581-92 pubmed..Our findings have direct implications for an understanding of the regulation and function of K6 during hyperproliferation in stratified epithelia and the search for disease-causing mutations in K6 sequences in the human population. ..
- McGowan K, Coulombe P. The wound repair-associated keratins 6, 16, and 17. Insights into the role of intermediate filaments in specifying keratinocyte cytoarchitecture. Subcell Biochem. 1998;31:173-204 pubmed
- Cangkrama M, Darido C, Georgy S, Partridge D, Auden A, Srivastava S, et al. Two Ancient Gene Families Are Critical for Maintenance of the Mammalian Skin Barrier in Postnatal Life. J Invest Dermatol. 2016;136:1438-1448 pubmed publisher..These findings define the molecular safeguards for barrier function that accompany the transition from intrauterine to terrestrial life. ..
- Bayo P, Sanchis A, Bravo A, Cascallana J, Buder K, Tuckermann J, et al. Glucocorticoid receptor is required for skin barrier competence. Endocrinology. 2008;149:1377-88 pubmed..Moreover, the epidermis of GR(+/dim) and GR(dim/dim) embryos appeared normal, thus suggesting that DNA-binding-independent actions of GR are sufficient to mediate epidermal and hair follicle development during embryogenesis. ..
- Nguyen H, Merrill B, Polak L, Nikolova M, Rendl M, Shaver T, et al. Tcf3 and Tcf4 are essential for long-term homeostasis of skin epithelia. Nat Genet. 2009;41:1068-75 pubmed publisher..We established roles for Tcf3 and Tcf4 in long-term maintenance and wound repair of both epidermis and hair follicles, suggesting that Tcf proteins have both Wnt-dependent and Wnt-independent roles in lineage determination. ..
- Celli G, LaRochelle W, Mackem S, Sharp R, Merlino G. Soluble dominant-negative receptor uncovers essential roles for fibroblast growth factors in multi-organ induction and patterning. EMBO J. 1998;17:1642-55 pubmed
- Georgy S, Cangkrama M, Srivastava S, Partridge D, Auden A, Dworkin S, et al. Identification of a Novel Proto-oncogenic Network in Head and Neck Squamous Cell Carcinoma. J Natl Cancer Inst. 2015;107: pubmed publisher..84 X 10(3), P = .003) and human HNSCC cells. We defined a novel molecular signature in mammalian HNSCC, suggesting new treatment strategies targeting the GRHL3/GSK3B/c-MYC proto-oncogenic network. ..
- Sun P, Watanabe K, Fallahi M, Lee B, Afetian M, Rhéaume C, et al. Pygo2 regulates ?-catenin-induced activation of hair follicle stem/progenitor cells and skin hyperplasia. Proc Natl Acad Sci U S A. 2014;111:10215-20 pubmed publisher..These findings identify Pygo2 as an important regulator of Wnt/?-catenin function in skin epithelia and p53 activation as a prominent downstream event of ?-catenin/Pygo2 action in stem cell activation. ..