Homeodomain-only protein HOP is a novel modulator of late differentiation in keratinocytes.
The homeodomain-only protein (HOP) contains an atypical homeodomain which is unable to bind to DNA due to mutations in residues important for DNA binding. Recently, HOP was reported to regulate proliferation/differentiation homeostasis in different cell types. In the present study, we performed transcriptional profiling of cultured primary human keratinocytes and noted a robust induction of HOP upon calcium-induced cell differentiation. Immunohistochemistry of human skin localized HOP to the granular layer in the epidermis. Overexpression of HOP using a lentiviral vector up-regulated FLG and LOR expression during keratinocyte differentiation. Conversely, decreasing HOP expression using small interfering RNA markedly reduced the calcium-induced expression of late markers of differentiation in vitro, with the most prominent effect on profilaggrin (FLG) mRNA. Moreover, mRNA levels of profilaggrin and loricrin were downregulated in the epidermis of HOP knockout mice. Analysis of skin disorders revealed altered HOP expression in lichen planus, psoriasis and squamous cell carcinoma (SCC). Our data indicate that HOP is a novel modulator of late terminal differentiation in keratinocytes.
Department of Dermatology, University Hospital of Lausanne (CHUV), CH-1011 Lausanne, Switzerland.
Magdalena
M
Obarzanek-Fojt
Bertrand
B
Favre
Magdalini
M
Kypriotou
Stephan
S
Ryser
Marcel
M
Huber
Daniel
D
Hohl
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D002454:Cell Differentiation; D002478:Cells, Cultured; D000078404:Epidermal Cells; D004817:Epidermis / Q000254:growth & development; D000091344:Filaggrin Proteins; D020869:Gene Expression Profiling; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics; D015603:Keratinocytes / Q000166:cytology*; D008010:Lichen Planus / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D011565:Psoriasis / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D012867:Skin / Q000166:cytology / Q000254:growth & development; D012878:Skin Neoplasms / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
C000717249:FLG protein, human; D000091344:Filaggrin Proteins; C476884:HOPX protein, human; D018398:Homeodomain Proteins; D007381:Intermediate Filament Proteins; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; C064554:loricrin; D002118:Calcium