Role of the Transcriptional Repressor Zinc Finger with KRAB and SCAN Domains 3 (ZKSCAN3) in Retinal Pigment Epithelial Cells
Lysosomes are important for proper functioning of the retinal pigment epithelial (RPE) cells. RPE cells have a daily burden of phagocytosis of photoreceptor outer segments (POS) and also degrade cellular waste by autophagy. Here, we identified the role of Zinc-finger protein with KRAB and SCAN domai...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-09-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/10/2504 |
| _version_ | 1797515029647458304 |
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| author | Hsuan-Yeh Pan Mallika Valapala |
| author_facet | Hsuan-Yeh Pan Mallika Valapala |
| author_sort | Hsuan-Yeh Pan |
| collection | DOAJ |
| description | Lysosomes are important for proper functioning of the retinal pigment epithelial (RPE) cells. RPE cells have a daily burden of phagocytosis of photoreceptor outer segments (POS) and also degrade cellular waste by autophagy. Here, we identified the role of Zinc-finger protein with KRAB and SCAN domains 3 (ZKSCAN3) in co-ordinate regulation of lysosomal function and autophagy in the RPE. Our studies show that in the RPE, ZKSCAN3 is predominantly nuclear in healthy cells and its nuclear expression is reduced upon nutrient deprivation. siRNA-mediated knockdown of ZKSCAN3 results in de-repression of some of the ZKSCAN3 target genes. Knockdown of ZKSCAN3 also resulted in an induction in autophagy flux, increase in the number of functional lysosomes and accompanied activation of lysosomal cathepsin B activity in ARPE-19 cells. We also demonstrated that inhibition of P38 mitogen-activated protein kinase (MAPK) retains ZKSCAN3 in the nucleus in nutrient-deprived cells. In summary, our studies elucidated the role of ZKSCAN3 as a transcriptional repressor of autophagy and lysosomal function in the RPE. |
| first_indexed | 2024-03-10T06:40:47Z |
| format | Article |
| id | doaj.art-bc6600ff26c849b3bc2947572da04ea5 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T06:40:47Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-bc6600ff26c849b3bc2947572da04ea52023-11-22T17:44:42ZengMDPI AGCells2073-44092021-09-011010250410.3390/cells10102504Role of the Transcriptional Repressor Zinc Finger with KRAB and SCAN Domains 3 (ZKSCAN3) in Retinal Pigment Epithelial CellsHsuan-Yeh Pan0Mallika Valapala1School of Optometry, Indiana University, Bloomington, IN 47405, USASchool of Optometry, Indiana University, Bloomington, IN 47405, USALysosomes are important for proper functioning of the retinal pigment epithelial (RPE) cells. RPE cells have a daily burden of phagocytosis of photoreceptor outer segments (POS) and also degrade cellular waste by autophagy. Here, we identified the role of Zinc-finger protein with KRAB and SCAN domains 3 (ZKSCAN3) in co-ordinate regulation of lysosomal function and autophagy in the RPE. Our studies show that in the RPE, ZKSCAN3 is predominantly nuclear in healthy cells and its nuclear expression is reduced upon nutrient deprivation. siRNA-mediated knockdown of ZKSCAN3 results in de-repression of some of the ZKSCAN3 target genes. Knockdown of ZKSCAN3 also resulted in an induction in autophagy flux, increase in the number of functional lysosomes and accompanied activation of lysosomal cathepsin B activity in ARPE-19 cells. We also demonstrated that inhibition of P38 mitogen-activated protein kinase (MAPK) retains ZKSCAN3 in the nucleus in nutrient-deprived cells. In summary, our studies elucidated the role of ZKSCAN3 as a transcriptional repressor of autophagy and lysosomal function in the RPE.https://www.mdpi.com/2073-4409/10/10/2504autophagylysosomal functionzinc finger with KRAB and SCAN domains 3 (ZKSCAN3)retinal pigment epithelium (RPE) |
| spellingShingle | Hsuan-Yeh Pan Mallika Valapala Role of the Transcriptional Repressor Zinc Finger with KRAB and SCAN Domains 3 (ZKSCAN3) in Retinal Pigment Epithelial Cells Cells autophagy lysosomal function zinc finger with KRAB and SCAN domains 3 (ZKSCAN3) retinal pigment epithelium (RPE) |
| title | Role of the Transcriptional Repressor Zinc Finger with KRAB and SCAN Domains 3 (ZKSCAN3) in Retinal Pigment Epithelial Cells |
| title_full | Role of the Transcriptional Repressor Zinc Finger with KRAB and SCAN Domains 3 (ZKSCAN3) in Retinal Pigment Epithelial Cells |
| title_fullStr | Role of the Transcriptional Repressor Zinc Finger with KRAB and SCAN Domains 3 (ZKSCAN3) in Retinal Pigment Epithelial Cells |
| title_full_unstemmed | Role of the Transcriptional Repressor Zinc Finger with KRAB and SCAN Domains 3 (ZKSCAN3) in Retinal Pigment Epithelial Cells |
| title_short | Role of the Transcriptional Repressor Zinc Finger with KRAB and SCAN Domains 3 (ZKSCAN3) in Retinal Pigment Epithelial Cells |
| title_sort | role of the transcriptional repressor zinc finger with krab and scan domains 3 zkscan3 in retinal pigment epithelial cells |
| topic | autophagy lysosomal function zinc finger with KRAB and SCAN domains 3 (ZKSCAN3) retinal pigment epithelium (RPE) |
| url | https://www.mdpi.com/2073-4409/10/10/2504 |
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