Protein kinase C delta and eta differently regulate the expression of loricrin and Jun family proteins in human keratinocytes.
Barrier function of the epidermis is maintained by precise expression of keratinocyte-specific structural proteins to form the cornified cell envelope (CE). Loricrin, a major component of the CE, is expressed at the late stage of keratinocyte differentiation. In this study, we reveal the isoform-specific function of protein kinase C (PKC) in the regulation of loricrin expression. Both PKCdelta and PKCeta have been recognized as differentiation-promoting isoforms. However, loricrin expression was inversely controlled by PKCdelta and PKCeta in cultured keratinocytes and 3D skin culture; i.e. loricrin expression was decreased by PKCdelta and increased by PKCeta. To clarify the mechanisms that PKCdelta and PKCeta oppositely regulate the loricrin expression, we examined the expression of activator protein-1 (AP-1) family proteins, which modulate the transcription of loricrin and are downstream molecules of PKC. PKCdelta decreased c-Jun expression, whereas PKCeta increased JunD, which are positive regulators of loricrin transcription. These findings suggest that inverse effects of PKCdelta and PKCeta on loricrin expression attributes to the expression of c-Jun and JunD.
Kamioka
Nagisa
N
Institute of Molecular Oncology, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
Akahane
Tomoko
T
Kohno
Yoko
Y
Kuroki
Toshio
T
Iijima
Masafumi
M
Honma
Ikuo
I
Ohba
Motoi
M
D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics*; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D051745:Protein Kinase C-delta / Q000235:genetics / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*
D008565:Membrane Proteins; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; C064554:loricrin; C081975:protein kinase C eta; D011493:Protein Kinase C; D051745:Protein Kinase C-delta