title: Lipin-1 expression is critical for keratinocyte differentiation.
abstract: Lipin-1 is an Mg(2+)-dependent phosphatidate phosphatase that facilitates the dephosphorylation of phosphatidic acid to generate diacylglycerol. Little is known about the expression and function of lipin-1 in normal human epidermal keratinocytes (NHEKs). Here, we demonstrate that lipin-1 is present in basal and spinous layers of the normal human epidermis, and lipin-1 expression is gradually downregulated during NHEK differentiation. Interestingly, lipin-1 knockdown (KD) inhibited keratinocyte differentiation and caused G1 arrest by upregulating p21 expression. Cell cycle arrest by p21 is required for commitment of keratinocytes to differentiation, but must be downregulated for the progress of keratinocyte differentiation. Therefore, reduced keratinocyte differentiation results from sustained upregulation of p21 by lipin-1 KD. Lipin-1 KD also decreased the phosphorylation/activation of protein kinase C (PKC)α, whereas lipin-1 overexpression increased PKCα phosphorylation. Treatment with PKCα inhibitors, like lipin-1 KD, stimulated p21 expression, while lipin-1 overexpression reduced p21 expression, implicating PKCα in lipin-1-induced regulation of p21 expression. Taken together, these results suggest that lipin-1-mediated downregulation of p21 is critical for the progress of keratinocyte differentiation after the initial commitment of keratinocytes to differentiation induced by p21, and that PKCα is involved in p21 expression regulation by lipin-1.
authors.affiliation: Bioscience Research Institute, Amorepacific Corporation R&D Center, Yongin-si, Gyeonggi-do, Republic of Korea.
authors.forename: Minjung
authors.initials: M
authors.lastname: Chae
authors.affiliation: Bioscience Research Institute, Amorepacific Corporation R&D Center, Yongin-si, Gyeonggi-do, Republic of Korea.
authors.forename: Ji-Yong
authors.initials: JY
authors.lastname: Jung
authors.affiliation: Bioscience Research Institute, Amorepacific Corporation R&D Center, Yongin-si, Gyeonggi-do, Republic of Korea.
authors.forename: Il-Hong
authors.initials: IH
authors.lastname: Bae
authors.affiliation: Bioscience Research Institute, Amorepacific Corporation R&D Center, Yongin-si, Gyeonggi-do, Republic of Korea.
authors.forename: Hyoung-June
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Bioscience Research Institute, Amorepacific Corporation R&D Center, Yongin-si, Gyeonggi-do, Republic of Korea biopang@amorepacific.com TRLee@amorepacific.com.
authors.forename: Tae Ryong
authors.initials: TR
authors.lastname: Lee
authors.affiliation: Bioscience Research Institute, Amorepacific Corporation R&D Center, Yongin-si, Gyeonggi-do, Republic of Korea biopang@amorepacific.com TRLee@amorepacific.com.
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Shin
mesh_terms: D002453:Cell Cycle; D002454:Cell Differentiation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D015536:Down-Regulation; D004789:Enzyme Activation; D000078404:Epidermal Cells; D015971:Gene Expression Regulation, Enzymologic; D055785:Gene Knockdown Techniques; D006801:Humans; D007231:Infant, Newborn; D015603:Keratinocytes / Q000166:cytology*; D010711:Phosphatidate Phosphatase / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D051571:Protein Kinase C-alpha / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D004075:Diglycerides; D016159:Tumor Suppressor Protein p53; D051571:Protein Kinase C-alpha; C485999:LPIN1 protein, human; D010711:Phosphatidate Phosphatase
keywords: G1 arrest; keratin 1; keratin 10; p21; protein kinase Cα