Dysregulation of ubiquitin ligases in cancer

Ubiquitin ligases (UBLs) are critical components of the ubiquitin proteasome system (UPS), which governs fundamental processes regulating normal cellular homeostasis, metabolism, and cell cycle in response to external stress signals and DNA damage. Among multiple steps of the UPS system required to...

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Vydané v:	Drug resistance updates Ročník 23; s. 1 - 11
Hlavní autori:	Qi, Jianfei, Ronai, Ze’ev A.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	Scotland Elsevier Ltd 01.11.2015
Predmet:	Antineoplastic Agents - therapeutic use Cell Cycle - genetics Cell Transformation, Neoplastic - genetics Cell Transformation, Neoplastic - metabolism Cell Transformation, Neoplastic - pathology Epigenesis, Genetic Gene Expression Regulation, Neoplastic Hematology, Oncology and Palliative Medicine Humans Infectious Disease Neoplasms - drug therapy Neoplasms - genetics Neoplasms - metabolism Neoplasms - pathology Oncogene Proteins - genetics Oncogene Proteins - metabolism Proteasome Endopeptidase Complex - genetics Proteasome Endopeptidase Complex - metabolism Protein Processing, Post-Translational Proteolysis Signal Transduction Tumor Suppressor Proteins - genetics Tumor Suppressor Proteins - metabolism Ubiquitin - genetics Ubiquitin - metabolism Ubiquitin-Protein Ligases - genetics Ubiquitin-Protein Ligases - metabolism Ubiquitination
ISSN:	1368-7646, 1532-2084, 1532-2084
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Popis
Shrnutí:	Ubiquitin ligases (UBLs) are critical components of the ubiquitin proteasome system (UPS), which governs fundamental processes regulating normal cellular homeostasis, metabolism, and cell cycle in response to external stress signals and DNA damage. Among multiple steps of the UPS system required to regulate protein ubiquitination and stability, UBLs define specificity, as they recognize and interact with substrates in a temporally- and spatially-regulated manner. Such interactions are required for substrate modification by ubiquitin chains, which marks proteins for recognition and degradation by the proteasome or alters their subcellular localization or assembly into functional complexes. UBLs are often deregulated in cancer, altering substrate availability or activity in a manner that can promote cellular transformation. Such deregulation can occur at the epigenetic, genomic, or post-translational levels. Alterations in UBL can be used to predict their contributions, affecting tumor suppressors or oncogenes in select tumors. Better understanding of mechanisms underlying UBL expression and activities is expected to drive the development of next generation modulators that can serve as novel therapeutic modalities. This review summarizes our current understanding of UBL deregulation in cancer and highlights novel opportunities for therapeutic interventions.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 ObjectType-Review-3 content type line 23
ISSN:	1368-7646 1532-2084 1532-2084
DOI:	10.1016/j.drup.2015.09.001