HAUSP Is a Key Epigenetic Regulator of the Chromatin Effector Proteins

Abstract

HAUSP (herpes virus-associated ubiquitin-specific protease), also known as Ubiquitin Specific Protease 7, plays critical roles in cellular processes, such as chromatin biology and epigenetics, through the regulation of different signaling pathways. HAUSP is a main partner of the “Epigenetic Code Replication Machinery,” ECREM, a large protein complex that includes several epigenetic players, such as the ubiquitin-like containing plant homeodomain (PHD) and an interesting new gene (RING), finger domains 1 (UHRF1), as well as DNA methyltransferase 1 (DNMT1), histone deacetylase 1 (HDAC1), histone methyltransferase G9a, and histone acetyltransferase TIP60. Due to its deubiquitinase activity and its ability to team up through direct interactions with several epigenetic regulators, mainly UHRF1, DNMT1, TIP60, the histone lysine methyltransferase EZH2, and the lysine-specific histone demethylase LSD1, HAUSP positions itself at the top of the regulatory hierarchies involved in epigenetic silencing of tumor suppressor genes in cancer. This review highlights the increasing role of HAUSP as an epigenetic master regulator that governs a set of epigenetic players involved in both the maintenance of DNA methylation and histone post-translational modifications.

Roles of post-translational modifications of UHRF1 in cancer

“…USP7 safeguards UHRF1 from proteasomal degradation by engaging with its SRA domain through the TRAF-like domain. This interaction is crucial for the maintenance of DNA methylation [ 53 ]. Additionally, HSP90 inhibitors have been reported to induce UHRF1 ubiquitination-mediated protein degradation, thereby inhibiting cancer cell proliferation [ 54 ].…”

The Role of LSD1 and LSD2 in Cancers of the Gastrointestinal System: An Update

“…Sun et al investigated the potential mechanisms of HOXA11-AS and LSD1 in GC cells, concluding that HOXA11-AS RNAs are more prevalent in the nucleus of a panel of GC cells [30]. Additionally, it was predicted that lncRNA HOXA11-AS mediates EZH2 and LSD1 interaction [31]. At the same time, DNMT1, EZH2, and LSD1 are also likely to be recruited by other sequence-specific transcription factors [32].…”