Cargando…
The role of PML ubiquitination in human malignancies
Tumor suppressors are frequently downregulated in human cancers and understanding of the mechanisms through which tumor cells restrict the expression of tumor suppressors is important for the prognosis and intervention of diseases. The promyelocytic leukemia (PML) protein plays a critical role in mu...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3438505/ https://www.ncbi.nlm.nih.gov/pubmed/22935031 http://dx.doi.org/10.1186/1423-0127-19-81 |
_version_ | 1782242922513563648 |
---|---|
author | Chen, Ruey-Hwa Lee, Yu-Ru Yuan, Wei-Chien |
author_facet | Chen, Ruey-Hwa Lee, Yu-Ru Yuan, Wei-Chien |
author_sort | Chen, Ruey-Hwa |
collection | PubMed |
description | Tumor suppressors are frequently downregulated in human cancers and understanding of the mechanisms through which tumor cells restrict the expression of tumor suppressors is important for the prognosis and intervention of diseases. The promyelocytic leukemia (PML) protein plays a critical role in multiple tumor suppressive functions, such as growth inhibition, apoptosis, replicative senescence, suppression of oncogenic transformation, and inhibition of migration and angiogenesis. These tumor suppression functions are recapitulated in several mouse models. The expression of PML protein is frequently downregulated in diverse types of human tumors and this downregulation often correlates with tumor progression. Recent evidence has emerged that PML is aberrantly degraded in various types of tumors through ubiquitination-dependent mechanisms. Here, we summarize our current understanding of the PML ubiquitination/degradation pathways in human cancers. We point out that multiple pathways lead to PML ubiquitination and degradation. Furthermore, the PML ubiquitination processes are often dependent on other types of posttranslational modifications, such as phosphorylation, prolylisomerization, and sumoylation. Such feature indicates a highly regulated nature of PML ubiquitination in different cellular conditions and cell contexts, thus providing many avenues of opportunity to intervene PML ubiquitination pathways. We discuss the potential of targeting PML ubiquitination pathways for anti-cancer therapeutic strategies. |
format | Online Article Text |
id | pubmed-3438505 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-34385052012-09-12 The role of PML ubiquitination in human malignancies Chen, Ruey-Hwa Lee, Yu-Ru Yuan, Wei-Chien J Biomed Sci Review Tumor suppressors are frequently downregulated in human cancers and understanding of the mechanisms through which tumor cells restrict the expression of tumor suppressors is important for the prognosis and intervention of diseases. The promyelocytic leukemia (PML) protein plays a critical role in multiple tumor suppressive functions, such as growth inhibition, apoptosis, replicative senescence, suppression of oncogenic transformation, and inhibition of migration and angiogenesis. These tumor suppression functions are recapitulated in several mouse models. The expression of PML protein is frequently downregulated in diverse types of human tumors and this downregulation often correlates with tumor progression. Recent evidence has emerged that PML is aberrantly degraded in various types of tumors through ubiquitination-dependent mechanisms. Here, we summarize our current understanding of the PML ubiquitination/degradation pathways in human cancers. We point out that multiple pathways lead to PML ubiquitination and degradation. Furthermore, the PML ubiquitination processes are often dependent on other types of posttranslational modifications, such as phosphorylation, prolylisomerization, and sumoylation. Such feature indicates a highly regulated nature of PML ubiquitination in different cellular conditions and cell contexts, thus providing many avenues of opportunity to intervene PML ubiquitination pathways. We discuss the potential of targeting PML ubiquitination pathways for anti-cancer therapeutic strategies. BioMed Central 2012-08-30 /pmc/articles/PMC3438505/ /pubmed/22935031 http://dx.doi.org/10.1186/1423-0127-19-81 Text en Copyright ©2012 Chen et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Review Chen, Ruey-Hwa Lee, Yu-Ru Yuan, Wei-Chien The role of PML ubiquitination in human malignancies |
title | The role of PML ubiquitination in human malignancies |
title_full | The role of PML ubiquitination in human malignancies |
title_fullStr | The role of PML ubiquitination in human malignancies |
title_full_unstemmed | The role of PML ubiquitination in human malignancies |
title_short | The role of PML ubiquitination in human malignancies |
title_sort | role of pml ubiquitination in human malignancies |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3438505/ https://www.ncbi.nlm.nih.gov/pubmed/22935031 http://dx.doi.org/10.1186/1423-0127-19-81 |
work_keys_str_mv | AT chenrueyhwa theroleofpmlubiquitinationinhumanmalignancies AT leeyuru theroleofpmlubiquitinationinhumanmalignancies AT yuanweichien theroleofpmlubiquitinationinhumanmalignancies AT chenrueyhwa roleofpmlubiquitinationinhumanmalignancies AT leeyuru roleofpmlubiquitinationinhumanmalignancies AT yuanweichien roleofpmlubiquitinationinhumanmalignancies |