Deciphering structure, function and mechanism of lysine acetyltransferase HBO1 in protein acetylation, transcription regulation, DNA replication and its oncogenic properties in cancer.

Deciphering structure, function and mechanism of lysine acetyltransferase HBO1 in protein acetylation, transcription regulation, DNA replication and its oncogenic properties in cancer. Cell Mol Life Sci. 2019 Sep 18;: Authors: Lan R, Wang Q Abstract HBO1 complexes are major acetyltransferase responsible for histone H4 acetylation in vivo, which belongs to the MYST family. As the core catalytic subunit, HBO1 consists of an N-terminal domain and a C-terminal MYST domain that are in charge of acetyl-CoA binding and acetylation reaction. HBO1 complexes are multimeric and normally consist of two native subunits MEAF6, ING4 or ING5 and two kinds of cofactors as chromatin reader: Jade-1/2/3 and BRPF1/2/3. The choices of subunits to form the HBO1 complexes provide a regulatory switch to potentiate its activity between histone H4 and H3 tails. Thus, HBO1 complexes present multiple functions in histone acetylation, gene transcription, DNA replication, protein ubiquitination, and immune regulation, etc. HBO1 is a co-activator for CDT1 to facilitate chromatin loading of MCM complexes and promotes DNA replication licensing. This process is regulated by mitotic kinases such as CDK1 and PLK1 by phosphorylating HBO1 and modulating its acetyltransferase activity, therefore, connecting histone acetylation to regulations of cell cycle and DNA replication. In addition, both gene amplification and protein overexpression of HBO1 confirmed its oncogenic ro...
Source: Cellular and Molecular Life Sciences : CMLS - Category: Cytology Authors: Tags: Cell Mol Life Sci Source Type: research