- 作者: Ruey-Hwa Chen, Yu-Ru Lee and Wei-Chien Yuan
- 作者服務機構: Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan, R.O.C.
- 中文摘要: --
- 英文摘要:
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. - 中文關鍵字: --
- 英文關鍵字: PML, Ubiquitination, Tumor suppression