ASPP2 Is Phosphorylated by CDK1 during Mitosis and Required for Pancreatic Cancer Cell Proliferation
(1) Background: pancreatic cancer is highly lethal. The role of apoptosis-stimulating protein of p53-2 (ASPP2) in this lethal disease remains unclear. This protein belongs to the ASPP family of p53 interacting proteins. Previous studies in this lab used phosphate-binding tag (Phos-tag) sodium dodecy...
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MDPI AG
2023-11-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/22/5424 |
| _version_ | 1797459830158393344 |
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| author | Yi Xiao Yuanhong Chen Jianan Chen Jixin Dong |
| author_facet | Yi Xiao Yuanhong Chen Jianan Chen Jixin Dong |
| author_sort | Yi Xiao |
| collection | DOAJ |
| description | (1) Background: pancreatic cancer is highly lethal. The role of apoptosis-stimulating protein of p53-2 (ASPP2) in this lethal disease remains unclear. This protein belongs to the ASPP family of p53 interacting proteins. Previous studies in this lab used phosphate-binding tag (Phos-tag) sodium dodecyl sulfate (SDS) polyacrylamide gels and identified a motility upshift of the ASPP family of proteins during mitosis. (2) Purpose: this study expands on previous findings to identify the detailed phosphorylation regulation of ASPP2 during mitosis, as well as the function of ASPP2 in pancreatic cancer. (3) Methods: the Phos-tag technique was used to investigate the phosphorylation mechanism of ASPP2 during mitosis. Phospho-specific antibodies were generated to validate the phosphorylation of ASPP2, and ASPP2-inducible expression cell lines were established to determine the role of ASPP2 in pancreatic cancer. RNA sequencing (RNA-Seq) was used to uncover the downstream targets of ASPP2. (4) Results: results demonstrate that ASPP2 is phosphorylated during mitosis by cyclin-dependent kinase 1 (CDK1) at sites S562 and S704. In vitro and in vivo results show that ASPP2 is required for pancreatic cancer growth. Furthermore, the expressions of yes-associated protein (YAP)-related genes are found to be dramatically altered by ASPP2 depletion. Together, these findings reveal the phosphorylation mechanism of ASPP2 during mitosis. Collectively, results strongly indicate that ASPP2 is a potential target for abating tumor cell growth in pancreatic cancer. |
| first_indexed | 2024-03-09T16:56:33Z |
| format | Article |
| id | doaj.art-44d1d6adf75848d58c53cbc34bdf1c9a |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T16:56:33Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-44d1d6adf75848d58c53cbc34bdf1c9a2023-11-24T14:34:24ZengMDPI AGCancers2072-66942023-11-011522542410.3390/cancers15225424ASPP2 Is Phosphorylated by CDK1 during Mitosis and Required for Pancreatic Cancer Cell ProliferationYi Xiao0Yuanhong Chen1Jianan Chen2Jixin Dong3Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USAEppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USAEppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USAEppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA(1) Background: pancreatic cancer is highly lethal. The role of apoptosis-stimulating protein of p53-2 (ASPP2) in this lethal disease remains unclear. This protein belongs to the ASPP family of p53 interacting proteins. Previous studies in this lab used phosphate-binding tag (Phos-tag) sodium dodecyl sulfate (SDS) polyacrylamide gels and identified a motility upshift of the ASPP family of proteins during mitosis. (2) Purpose: this study expands on previous findings to identify the detailed phosphorylation regulation of ASPP2 during mitosis, as well as the function of ASPP2 in pancreatic cancer. (3) Methods: the Phos-tag technique was used to investigate the phosphorylation mechanism of ASPP2 during mitosis. Phospho-specific antibodies were generated to validate the phosphorylation of ASPP2, and ASPP2-inducible expression cell lines were established to determine the role of ASPP2 in pancreatic cancer. RNA sequencing (RNA-Seq) was used to uncover the downstream targets of ASPP2. (4) Results: results demonstrate that ASPP2 is phosphorylated during mitosis by cyclin-dependent kinase 1 (CDK1) at sites S562 and S704. In vitro and in vivo results show that ASPP2 is required for pancreatic cancer growth. Furthermore, the expressions of yes-associated protein (YAP)-related genes are found to be dramatically altered by ASPP2 depletion. Together, these findings reveal the phosphorylation mechanism of ASPP2 during mitosis. Collectively, results strongly indicate that ASPP2 is a potential target for abating tumor cell growth in pancreatic cancer.https://www.mdpi.com/2072-6694/15/22/5424pancreatic cancerASPP2CDK1YAPphosphorylationp53 |
| spellingShingle | Yi Xiao Yuanhong Chen Jianan Chen Jixin Dong ASPP2 Is Phosphorylated by CDK1 during Mitosis and Required for Pancreatic Cancer Cell Proliferation Cancers pancreatic cancer ASPP2 CDK1 YAP phosphorylation p53 |
| title | ASPP2 Is Phosphorylated by CDK1 during Mitosis and Required for Pancreatic Cancer Cell Proliferation |
| title_full | ASPP2 Is Phosphorylated by CDK1 during Mitosis and Required for Pancreatic Cancer Cell Proliferation |
| title_fullStr | ASPP2 Is Phosphorylated by CDK1 during Mitosis and Required for Pancreatic Cancer Cell Proliferation |
| title_full_unstemmed | ASPP2 Is Phosphorylated by CDK1 during Mitosis and Required for Pancreatic Cancer Cell Proliferation |
| title_short | ASPP2 Is Phosphorylated by CDK1 during Mitosis and Required for Pancreatic Cancer Cell Proliferation |
| title_sort | aspp2 is phosphorylated by cdk1 during mitosis and required for pancreatic cancer cell proliferation |
| topic | pancreatic cancer ASPP2 CDK1 YAP phosphorylation p53 |
| url | https://www.mdpi.com/2072-6694/15/22/5424 |
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