BAZ1B the Protean Protein

Abstract

The bromodomain adjacent to the zinc finger domain 1B (BAZ1B) or Williams syndrome transcription factor (WSTF) are just two of the names referring the same protein that is encoded by the WBSCR9 gene and is among the 26–28 genes that are lost from one copy of 7q11.23 in Williams syndrome (WS: OMIM 194050). Patients afflicted by this contiguous gene deletion disorder present with a range of symptoms including cardiovascular complications, developmental defects as well as a characteristic cognitive and behavioral profile. Studies in patients with atypical deletions and mouse models support BAZ1B hemizygosity as a contributing factor to some of the phenotypes. Focused analysis on BAZ1B has revealed this to be a versatile nuclear protein with a central role in chromatin remodeling through two distinct complexes as well as being involved in the replication and repair of DNA, transcriptional processes involving RNA Polymerases I, II, and III as well as possessing kinase activity. Here, we provide a comprehensive review to summarize the many aspects of BAZ1B function including its recent link to cancer.

Combinatorial targeting of a chromatin complex comprising Dot1L, menin and the tyrosine kinase BAZ1B reveals a new therapeutic vulnerability of endocrine therapy-resistant breast cancer

“…Interestingly, a bromodomain protein encoded by the Bromodomain Adjacent To Zinc Finger Domain 1B gene (BAZ1B), also known as WSTF (Williams Syndrome Transcription Factor), resulted as one of the central components of both complexes (Fig. 4 A) [ 53 ]. Given the role of bromodomain proteins as ‘readers’ of epigenetic marks that translates these signals into gene regulatory events, the interaction between Dot1L, menin and BAZ1B was experimentally validated by co-IP experiments in nuclear lysates from MCF-7 cells (Fig.…”

“…Among them, BAZ1B caught our attention being shared by both these complexes and associated with both Dot1L and menin on chromatin. BAZ1B is a versatile nuclear protein that, in addition to functioning as chromatin remodeler, has a protein tyrosine kinase activity [ 53 ] and has been involved in DNA replication and repair and transcriptional regulation. An oncogenic role of BAZ1B in cancers has been postulated via its phosphorylation and acetylation, where it has been proposed that its abnormal activity would favor cancer progression [ 53 ].…”

“…BAZ1B is a versatile nuclear protein that, in addition to functioning as chromatin remodeler, has a protein tyrosine kinase activity [ 53 ] and has been involved in DNA replication and repair and transcriptional regulation. An oncogenic role of BAZ1B in cancers has been postulated via its phosphorylation and acetylation, where it has been proposed that its abnormal activity would favor cancer progression [ 53 ]. Given the crucial role of chromatin accessibility and remodelers in endocrine resistance in BC [ 55 ], we characterized in detail the role of BAZ1B and the effects of its inhibition in the breast tumor subtype that express ERα.…”

“…Dot1L, menin and BAZ1B are functional to this aim, also when considering the possibility of a combinatorial targeting of two or all three these factors. In this respect, it is worth mentioning that BAZ1B bromodomain motive and atypical protein tyrosine kinase activity [ 53 ] are both prone to be targeted by small molecule inhibitors, for a novel pharmacological strategy to block this protein and thereby act on ESR1 expression.…”

Pan Cancer Insights into BAZ1B as a Prognostic and Immunological Marker

“…This gene is missing in Williams-Beuren syndrome, a developmental disorder caused by the deletion of multiple genes in 7q11.23 [5]. BAZ1B has been reported to play a major role in DNA replication, DNA damage repair, RNA transcription, and apoptosis [6]. In addition, it is aberrantly expressed and dysregulated in many cancers.…”