Ubiquitination is crucial for cellular processes,such as protein degradation,apoptosis,autophagy,and cell cycle progression.Dysregulation of the ubiquitination network accounts for the development of numerous diseases,including cancer.Thus,targeting ubiquitination is a promising strategy in cancer therapy.Both apoptosis and autophagy are involved in tumorigenesis and response to cancer therapy.Although both are categorized as types of cell death,autophagy is generally considered to have protective functions,including protecting cells from apoptosis under certain cellular stress conditions.This review highlights recent advances in understanding the regulation of apoptosis and autophagy by ubiquitination.
Histone modifications are proposed to constitute a ＂histone code＂ for epigenetic regulation of gene expression. However, recent studies demonstrate that histones have to be disassembled from chromatin during transcription. Recent evidence, though not conclusive, suggests that histories might be degradable after being removed from chromatin during transcription. Degradation of overexpressed excessive histones, instead of native histones, has been shown to be dependent on proteasomes and ubiquitination. Since the 26S proteasome usually recognizes polyubiquitinated substrates, it is critical to demonstrate whether degradation of histones is mediated by polyubiquitination. Unexpectedly, there is almost no evidence that any ubiquitin ligase can promote polyubiquitination-dependent degradation of constitutive histones. Meanwhile, acetylation and phosphorylation are also associated with histone degradation. This review attempts to summarize the current knowledge on the transcription-coupled degradation of histones and its regulation by posttranslational protein modifications.
