USP22‐mediated deubiquitination of PTEN inhibits pancreatic cancer progression by inducing p21 expression
Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a dual lipid and protein phosphatase. Multiple mechanisms contributing to the regulation of PTEN levels have been identified thus far, including post‐translational modifications, epigenetic mechanisms, and transcriptional mechanisms....
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-03-01
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| Series: | Molecular Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/1878-0261.13137 |
| _version_ | 1818487621068783616 |
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| author | Dianyun Ren Yan Sun Dan Li Heshui Wu Xin Jin |
| author_facet | Dianyun Ren Yan Sun Dan Li Heshui Wu Xin Jin |
| author_sort | Dianyun Ren |
| collection | DOAJ |
| description | Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a dual lipid and protein phosphatase. Multiple mechanisms contributing to the regulation of PTEN levels have been identified thus far, including post‐translational modifications, epigenetic mechanisms, and transcriptional mechanisms. In the present study, we identified ubiquitin‐specific peptidase 22 (USP22) as a novel deubiquitination‐modifying enzyme of PTEN. Furthermore, by inducing deubiquitination and inhibiting the degradation of PTEN, USP22 could induce cyclin‐dependent kinase inhibitor 1A (CDKN1A, also symboled as p21) expression in pancreatic cancer. Besides, MDM2 proto‐oncogene (MDM2) inhibitor enhanced the antipancreatic cancer effects of USP22 overexpression. In addition to its regulation of MDM2‐tumor protein p53 (p53) signaling, we found that PTEN could induce p21 expression by interacting with ankyrin repeat and KH domain containing 1 (ANKHD1) and inhibiting ANKHD1 binding to the p21 promoter. Taken together, our results indicate that ANKHD1 and MDM2 might be novel therapeutic targets in pancreatic cancer. |
| first_indexed | 2024-12-10T16:40:28Z |
| format | Article |
| id | doaj.art-975790c9321b458cb94e9676e8d72ab5 |
| institution | Directory Open Access Journal |
| issn | 1574-7891 1878-0261 |
| language | English |
| last_indexed | 2024-12-10T16:40:28Z |
| publishDate | 2022-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj.art-975790c9321b458cb94e9676e8d72ab52022-12-22T01:41:16ZengWileyMolecular Oncology1574-78911878-02612022-03-011651200121710.1002/1878-0261.13137USP22‐mediated deubiquitination of PTEN inhibits pancreatic cancer progression by inducing p21 expressionDianyun Ren0Yan Sun1Dan Li2Heshui Wu3Xin Jin4Department of Pancreatic Surgery Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Pancreatic Surgery Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaCardiovascular Medicine Department Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Pancreatic Surgery Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Urology The Second Xiangya Hospital Central South University Changsha ChinaPhosphatase and tensin homolog deleted on chromosome ten (PTEN) is a dual lipid and protein phosphatase. Multiple mechanisms contributing to the regulation of PTEN levels have been identified thus far, including post‐translational modifications, epigenetic mechanisms, and transcriptional mechanisms. In the present study, we identified ubiquitin‐specific peptidase 22 (USP22) as a novel deubiquitination‐modifying enzyme of PTEN. Furthermore, by inducing deubiquitination and inhibiting the degradation of PTEN, USP22 could induce cyclin‐dependent kinase inhibitor 1A (CDKN1A, also symboled as p21) expression in pancreatic cancer. Besides, MDM2 proto‐oncogene (MDM2) inhibitor enhanced the antipancreatic cancer effects of USP22 overexpression. In addition to its regulation of MDM2‐tumor protein p53 (p53) signaling, we found that PTEN could induce p21 expression by interacting with ankyrin repeat and KH domain containing 1 (ANKHD1) and inhibiting ANKHD1 binding to the p21 promoter. Taken together, our results indicate that ANKHD1 and MDM2 might be novel therapeutic targets in pancreatic cancer.https://doi.org/10.1002/1878-0261.13137ANKHD1p21pancreatic cancerPTENUSP22 |
| spellingShingle | Dianyun Ren Yan Sun Dan Li Heshui Wu Xin Jin USP22‐mediated deubiquitination of PTEN inhibits pancreatic cancer progression by inducing p21 expression Molecular Oncology ANKHD1 p21 pancreatic cancer PTEN USP22 |
| title | USP22‐mediated deubiquitination of PTEN inhibits pancreatic cancer progression by inducing p21 expression |
| title_full | USP22‐mediated deubiquitination of PTEN inhibits pancreatic cancer progression by inducing p21 expression |
| title_fullStr | USP22‐mediated deubiquitination of PTEN inhibits pancreatic cancer progression by inducing p21 expression |
| title_full_unstemmed | USP22‐mediated deubiquitination of PTEN inhibits pancreatic cancer progression by inducing p21 expression |
| title_short | USP22‐mediated deubiquitination of PTEN inhibits pancreatic cancer progression by inducing p21 expression |
| title_sort | usp22 mediated deubiquitination of pten inhibits pancreatic cancer progression by inducing p21 expression |
| topic | ANKHD1 p21 pancreatic cancer PTEN USP22 |
| url | https://doi.org/10.1002/1878-0261.13137 |
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