PMID- 26658689
OWN - NLM
STAT- MEDLINE
DCOM- 20161216
LR  - 20210217
IS  - 1539-7262 (Electronic)
IS  - 0022-2275 (Print)
IS  - 0022-2275 (Linking)
VI  - 57
IP  - 4
DP  - 2016 Apr
TI  - Lipin-1 expression is critical for keratinocyte differentiation.
PG  - 563-73
LID - 10.1194/jlr.M062588 [doi]
AB  - 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)alpha, whereas lipin-1 
      overexpression increased PKCalpha phosphorylation. Treatment with PKCalpha inhibitors, 
      like lipin-1 KD, stimulated p21 expression, while lipin-1 overexpression reduced 
      p21 expression, implicating PKCalpha 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 PKCalpha is 
      involved in p21 expression regulation by lipin-1.
CI  - Copyright (c) 2016 by the American Society for Biochemistry and Molecular Biology, 
      Inc.
FAU - Chae, Minjung
AU  - Chae M
AD  - Bioscience Research Institute, Amorepacific Corporation R&D Center, Yongin-si, 
      Gyeonggi-do, Republic of Korea.
FAU - Jung, Ji-Yong
AU  - Jung JY
AD  - Bioscience Research Institute, Amorepacific Corporation R&D Center, Yongin-si, 
      Gyeonggi-do, Republic of Korea.
FAU - Bae, Il-Hong
AU  - Bae IH
AD  - Bioscience Research Institute, Amorepacific Corporation R&D Center, Yongin-si, 
      Gyeonggi-do, Republic of Korea.
FAU - Kim, Hyoung-June
AU  - Kim HJ
AD  - Bioscience Research Institute, Amorepacific Corporation R&D Center, Yongin-si, 
      Gyeonggi-do, Republic of Korea.
FAU - Lee, Tae Ryong
AU  - Lee TR
AD  - Bioscience Research Institute, Amorepacific Corporation R&D Center, Yongin-si, 
      Gyeonggi-do, Republic of Korea biopang@amorepacific.com TRLee@amorepacific.com.
FAU - Shin, Dong Wook
AU  - Shin DW
AD  - Bioscience Research Institute, Amorepacific Corporation R&D Center, Yongin-si, 
      Gyeonggi-do, Republic of Korea biopang@amorepacific.com TRLee@amorepacific.com.
LA  - eng
PT  - Journal Article
DEP - 20151213
PL  - United States
TA  - J Lipid Res
JT  - Journal of lipid research
JID - 0376606
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Diglycerides)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 2.7.11.13 (Protein Kinase C-alpha)
RN  - EC 3.1.3.4 (LPIN1 protein, human)
RN  - EC 3.1.3.4 (Phosphatidate Phosphatase)
SB  - IM
MH  - Cell Cycle
MH  - *Cell Differentiation
MH  - Cyclin-Dependent Kinase Inhibitor p21/genetics/metabolism
MH  - Diglycerides/metabolism
MH  - Down-Regulation
MH  - Enzyme Activation
MH  - Epidermal Cells
MH  - *Gene Expression Regulation, Enzymologic
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Infant, Newborn
MH  - Keratinocytes/*cytology
MH  - Phosphatidate Phosphatase/deficiency/*genetics/*metabolism
MH  - Protein Kinase C-alpha/metabolism
MH  - Tumor Suppressor Protein p53/metabolism
PMC - PMC4808765
OTO - NOTNLM
OT  - G1 arrest
OT  - keratin 1
OT  - keratin 10
OT  - p21
OT  - protein kinase Calpha
EDAT- 2015/12/15 06:00
MHDA- 2016/12/17 06:00
PMCR- 2017/04/01
CRDT- 2015/12/15 06:00
PHST- 2015/08/08 00:00 [received]
PHST- 2015/12/15 06:00 [entrez]
PHST- 2015/12/15 06:00 [pubmed]
PHST- 2016/12/17 06:00 [medline]
PHST- 2017/04/01 00:00 [pmc-release]
AID - S0022-2275(20)35412-2 [pii]
AID - m062588 [pii]
AID - 10.1194/jlr.M062588 [doi]
PST - ppublish
SO  - J Lipid Res. 2016 Apr;57(4):563-73. doi: 10.1194/jlr.M062588. Epub 2015 Dec 13.