p53 -Dependent and -Independent Nucleolar Stress Responses
The nucleolus has emerged as a cellular stress sensor and key regulator of p53-dependent and -independent stress responses. A variety of abnormal metabolic conditions, cytotoxic compounds, and physical insults induce alterations in nucleolar structure and function, a situation known as nucleolar or...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2012-10-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | http://www.mdpi.com/2073-4409/1/4/774 |
| _version_ | 1797715942103318528 |
|---|---|
| author | Mikael S. Lindström Monica Nistér Karl Holmberg Olausson |
| author_facet | Mikael S. Lindström Monica Nistér Karl Holmberg Olausson |
| author_sort | Mikael S. Lindström |
| collection | DOAJ |
| description | The nucleolus has emerged as a cellular stress sensor and key regulator of p53-dependent and -independent stress responses. A variety of abnormal metabolic conditions, cytotoxic compounds, and physical insults induce alterations in nucleolar structure and function, a situation known as nucleolar or ribosomal stress. Ribosomal proteins, including RPL11 and RPL5, become increasingly bound to the p53 regulatory protein MDM2 following nucleolar stress. Ribosomal protein binding to MDM2 blocks its E3 ligase function leading to stabilization and activation of p53. In this review we focus on a number of novel regulators of the RPL5/RPL11-MDM2-p53 complex including PICT1 (GLTSCR2), MYBBP1A, PML and NEDD8. p53-independent pathways mediating the nucleolar stress response are also emerging and in particular the negative control that RPL11 exerts on Myc oncoprotein is of importance, given the role of Myc as a master regulator of ribosome biogenesis. We also briefly discuss the potential of chemotherapeutic drugs that specifically target RNA polymerase I to induce nucleolar stress. |
| first_indexed | 2024-03-12T08:14:16Z |
| format | Article |
| id | doaj.art-cc1d0baa4f594f1383ed29144346e92d |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T08:14:16Z |
| publishDate | 2012-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-cc1d0baa4f594f1383ed29144346e92d2023-09-02T19:00:31ZengMDPI AGCells2073-44092012-10-011477479810.3390/cells1040774p53 -Dependent and -Independent Nucleolar Stress ResponsesMikael S. LindströmMonica NistérKarl Holmberg OlaussonThe nucleolus has emerged as a cellular stress sensor and key regulator of p53-dependent and -independent stress responses. A variety of abnormal metabolic conditions, cytotoxic compounds, and physical insults induce alterations in nucleolar structure and function, a situation known as nucleolar or ribosomal stress. Ribosomal proteins, including RPL11 and RPL5, become increasingly bound to the p53 regulatory protein MDM2 following nucleolar stress. Ribosomal protein binding to MDM2 blocks its E3 ligase function leading to stabilization and activation of p53. In this review we focus on a number of novel regulators of the RPL5/RPL11-MDM2-p53 complex including PICT1 (GLTSCR2), MYBBP1A, PML and NEDD8. p53-independent pathways mediating the nucleolar stress response are also emerging and in particular the negative control that RPL11 exerts on Myc oncoprotein is of importance, given the role of Myc as a master regulator of ribosome biogenesis. We also briefly discuss the potential of chemotherapeutic drugs that specifically target RNA polymerase I to induce nucleolar stress.http://www.mdpi.com/2073-4409/1/4/774nucleolusp53ribosome biogenesiscancerRPL11 |
| spellingShingle | Mikael S. Lindström Monica Nistér Karl Holmberg Olausson p53 -Dependent and -Independent Nucleolar Stress Responses Cells nucleolus p53 ribosome biogenesis cancer RPL11 |
| title | p53 -Dependent and -Independent Nucleolar Stress Responses |
| title_full | p53 -Dependent and -Independent Nucleolar Stress Responses |
| title_fullStr | p53 -Dependent and -Independent Nucleolar Stress Responses |
| title_full_unstemmed | p53 -Dependent and -Independent Nucleolar Stress Responses |
| title_short | p53 -Dependent and -Independent Nucleolar Stress Responses |
| title_sort | p53 dependent and independent nucleolar stress responses |
| topic | nucleolus p53 ribosome biogenesis cancer RPL11 |
| url | http://www.mdpi.com/2073-4409/1/4/774 |
| work_keys_str_mv | AT mikaelslindstrom p53dependentandindependentnucleolarstressresponses AT monicanister p53dependentandindependentnucleolarstressresponses AT karlholmbergolausson p53dependentandindependentnucleolarstressresponses |