期刊
CANCERS
卷 13, 期 9, 页码 -出版社
MDPI
DOI: 10.3390/cancers13092226
关键词
RB family proteins; pocket proteins; cell cycle; phosphatase PP1; spinophilin; cancer; tumorigenesis
类别
资金
- Ministerio de Ciencia, Innovacion y Universidades (MCIU) Plan Estatal de I+D+I 2018, a la Agencia Estatal de Investigacion (AEI) y al Fondo Europeo de Desarrollo Regional (MCIU/AEI/FEDER) [RTI2018-097455-B-I00]
- AEI-MICIU/FEDER [RED2018-102723-T]
- CIBER de Cancer [CB16/12/00275]
- FEDER from Regional Development European Funds (European Union)
- Consejeria de Salud [PI-0397-2017]
- Consejeria of Economia, Conocimiento, Empresas y Universidad of the Junta de Andalucia [P18-RT-2501]
- Fundacion AECC
- Fundacion Eugenio Rodriguez Pascual
Cell cycle progression is highly regulated by modulating the phosphorylation status of the retinoblastoma protein and the other members of the RB family, with a balance between kinases and phosphatases. The PP1-Spinophilin holoenzyme has been identified as the main phosphatase responsible for dephosphorylating RB proteins, and it has been linked to tumor suppression and tumorigenesis in lung and breast cancers. This connection between the cell cycle, stem cell biology, and SPN/PP1/RB proteins has also been proposed.
Simple Summary Cell cycle progression is highly regulated by modulating the phosphorylation status of retinoblastoma (RB) family proteins. This process is controlled by a balance in the action of kinases, such as the complexes formed by cyclin-dependent kinases (CDKs) and cyclins, and phosphatases, mainly the protein phosphatase 1 (PP1). However, while the phosphorylation of the RB family has been largely studied, its dephosphorylation is less known. Recently, the PP1-Spinophilin (SPN) holoenzyme has been described as the main phosphatase responsible for the dephosphorylation of RB proteins during the G0/G1 transition and at the end of G1. Here, we describe the regulation of the phosphorylation status of RB family proteins, giving importance not only to their inactivation by phosphorylation but also to their dephosphorylation to restore the cell cycle. Cell cycle progression is highly regulated by modulating the phosphorylation status of the retinoblastoma protein (pRB) and the other two members of the RB family, p107 and p130. This process is controlled by a balance in the action of kinases, such as the complexes formed by cyclin-dependent kinases (CDKs) and cyclins, and phosphatases, mainly the protein phosphatase 1 (PP1). However, while the phosphorylation of the RB family has been largely studied, its dephosphorylation is less known. Phosphatases are holoenzymes formed by a catalytic subunit and a regulatory protein with substrate specificity. Recently, the PP1-Spinophilin (SPN) holoenzyme has been described as the main phosphatase responsible for the dephosphorylation of RB proteins during the G0/G1 transition and at the end of G1. Moreover, SPN has been described as a tumor suppressor dependent on PP1 in lung and breast tumors, where it promotes tumorigenesis by increasing the cancer stem cell pool. Therefore, a connection between the cell cycle and stem cell biology has also been proposed via SPN/PP1/RB proteins.
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