Keratin 14 is a novel interaction partner of keratinocyte differentiation regulator:receptor-interacting protein kinase 4

Authors

CEREN SÜMER
ASİYE BÜŞRA BOZ ER
TUBA DİNÇER

DOI

10.3906/biy-1904-37

Abstract

The epidermis, the outer layer of the skin, is formed by stratified keratinocyte layers. The self-renewal of the epidermis is provided by sustained proliferation and differentiation of the keratinocyte stem cells localized to the basal layer of the epidermis. Receptorinteracting protein kinase 4 (RIPK4) is an important regulator of keratinocyte differentiation, mutations of which are associated with congenital ectodermal malformations. In an attempt to identify the molecular basis of RIPK4's function, we applied yeast two-hybrid screen (Y2H) and found basal layer-specific keratin filament component keratin 14 (KRT14) as a novel RIPK4-interacting partner. During keratinocyte differentiation, layer-specific keratin composition is tightly regulated. Likewise, the basal layer specific KRT14/keratin 5 (KRT5) heterodimers are replaced by keratin 1 (KRT1)/keratin 10 (KRT10) in suprabasal layers. The regulation of keratin turnover is under the control of signaling associated with posttranslational modifications in which phosphorylation plays a major role. In this study, we verified the KRT14-RIPK4 interaction, which was identified with Y2H, in mammalian cells and showed that the interaction was direct by using proteins expressed in bacteria. According to our results, the N-terminal kinase domain of RIPK4 is responsible for KRT14-RIPK4 interaction; however, the RIPK4 kinase activity is dispensable for the interaction. In accordance with their interaction, RIPK4 and KRT14 colocalize within the cells, particularly at keratin filaments associated with perinuclear ring-like structures. Moreover, RIPK4 did not show any effect on KRT14/KRT5 heterodimer formation. Our results suggest that RIPK4 may regulate the keratin turnover required for keratinocyte differentiation through interacting with KRT14.

Keywords

Keratins, keratinocyte differentiation, RIPK4, protein-protein interactions

First Page

225

Last Page

234

Recommended Citation

SÜMER, CEREN; ER, ASİYE BÜŞRA BOZ; and DİNÇER, TUBA (2019) "Keratin 14 is a novel interaction partner of keratinocyte differentiation regulator:receptor-interacting protein kinase 4," Turkish Journal of Biology: Vol. 43: No. 4, Article 1. https://doi.org/10.3906/biy-1904-37
Available at: https://journals.tubitak.gov.tr/biology/vol43/iss4/1