Modulation of Nuclear Receptor Function by Chromatin Modifying Factor TIP60

Abstract

Nuclear receptors (NRs) are transcription factors that bind to specific DNA sequences known as hormone response elements located upstream of their target genes. Transcriptional activity of NRs can be modulated by binding of the compatible ligand and transient interaction with cellular coregulators, functioning either as coactivators or as corepressors. Many coactivator proteins possess intrinsic histone acetyltransferase (HAT) activity that catalyzes the acetylation of specific lysine residues in histone tails and loosens the histone-DNA interaction, thereby facilitating access of transcriptional factors to the regulatory sequences of the DNA. Tat interactive protein 60 (TIP60), a member of the Mof-Ybf2-Sas2-TIP60 family of HAT protein, is a multifunctional coregulator that controls a number of physiological processes including apoptosis, DNA damage repair, and transcriptional regulation. Over the last two decades or so, TIP60 has been extensively studied for its role as NR coregulator, controlling various aspect of steroid receptor functions. The aim of this review is to summarize the findings on the role of TIP60 as a coregulator for different classes of NRs and its overall functional implications. We also discuss the latest studies linking TIP60 to NR-associated metabolic disorders and cancers for its potential use as a therapeutic drug target in future.

Mechanisms Mediating the Regulation of Peroxisomal Fatty Acid Beta-Oxidation by PPARα

“…The ligand-independent coregulators (heat-shock protein-70) could also prevent the PPARα from proteolytic degradation in the cytosol before PPARα could translocate to the nucleus in the activated state [131] and, typically, these proteins bind to the hinge region of the nuclear receptor that interconnects the DNA binding region to the ligand-binding region of the receptor [127]. The activators, on the other hand, could help PPARα zero in onto the specific PPREs of the target genomic region, help attach it to the PPREs with the assistance of nucleosomal-specific functions such as histone methylases (SRC proteins) [142], histone acetyltransferases (CBP/p300) [143,144], DNA-helicases [145], PRIC285 [124], and PRIC320 [146]. The activators would also function by stabilizing the transcriptional complex (PRIP/ASC2 [147]) and potentiate the recruitment of RNA-polymerase complex proteins to the transitional complex (mediator complex, PBP [148,149] (Figure 7B).…”

Sex steroid hormone function in the brain niche: Implications for brain metastatic colonization and progression

“…This enables recruitment of histone acetyltransferases, coactivators, and other proteins crucial for transcriptional machinery. [87][88][89] Some studies suggest that MISS can be induced by testosterone; however, whether this occurs via membrane-bound AR or an unknown receptor remains unclear. 83,90,91 Estrogens are well known to play a mitogenic role in breast cancer via direct activation of ERα and endocrine therapy (ie, Selective ER Modulators, ER-antagonists, and aromatase inhibitors) are the main form of targeted therapy for these tumors.…”

“…Following ligand‐binding, AR translocates to the nucleus to bind androgen response elements. This enables recruitment of histone acetyltransferases, coactivators, and other proteins crucial for transcriptional machinery 87‐89 . Some studies suggest that MISS can be induced by testosterone; however, whether this occurs via membrane‐bound AR or an unknown receptor remains unclear 83,90,91 …”

Interaction of Nuclear Export Protein with G Protein Pathway Suppressor 2 (GPS2) Facilitates Influenza A Virus Replication by Weakening the Inhibition of GPS2 to RNA Synthesis and Ribonucleoprotein Assembly

“…Influenza A virus (IAV) is a serious public health concern that causes annual seasonal epidemics and even sporadic pandemics, leading to severe morbidity and mortality worldwide ( 1 , 2 ). IAV is responsible for approximately 290,000 to 650,000 deaths each year worldwide ( http://www.who.int/topics/influenza/en/ ), and young children and elderly individuals are highly vulnerable to infection.…”