Lysine Acetyltransferases and Their Role in AR Signaling and Prostate Cancer.

The development and growth of a normal prostate gland, as well as its physiological functions, are regulated by the actions of androgens through androgen receptor (AR) signaling which drives multiple cellular processes including transcription, cellular proliferation, and apoptosis in prostate cells. Post-translational regulation of AR plays a vital role in directing its cellular activities modulating its stability, nuclear localization, and transcriptional activity. Among various post-translational modifications (PTMs), acetylation is an essential PTM recognized in AR and is governed by the regulated actions of acetyltransferases and deacetyltransferases.

TIP60 acts as a regulator of genes involved in filopodia formation and cell migration during wound healing.

Wound healing is a complex phenomenon that requires coordination of numerous molecular and cellular changes to facilitate timely and efficient repair of the damaged tissue. Although many of these molecular pathways have been detailed, others remain to be elucidated. In the present work, we show for the first time, roles for the acetyltransferase TIP60 and nuclear receptor transcription factor PXR in this process, participating in wound healing by altering actin dynamics and cellular motility.

Modulation of Nuclear Receptor Function by Chromatin Modifying Factor TIP60.

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.

Heterodimerization of Retinoid X Receptor with Xenobiotic Receptor partners occurs in the cytoplasmic compartment: Mechanistic insights of events in living cells.

Retinoid X Receptor (RXR) serves as the heterodimeric partner of two major xenobiotic nuclear receptors, Pregnane and Xenobiotic Receptor (PXR) and Constitutive Androstane Receptor (CAR). These receptors are primarily involved in the metabolism and clearance of endobiotics and xenobiotics (including clinical drugs) from the body. Here, we report for the first time that intermolecular interactions between RXR-PXR and RXR-CAR occurs in the cytoplasmic compartment of the cell in a ligand-independent manner.

Novel complex of HAT protein TIP60 and nuclear receptor PXR promotes cell migration and adhesion.

PXR is a member of nuclear receptor superfamily and a well-characterized mediator of xenobiotic metabolism. The classical mode of PXR activation involves its binding to appropriate ligand and subsequent heterodimerization with its partner RXR. However, various factors such as post-translational modifications and crosstalk with different cellular factors may also regulate the functional dynamics and behavior of PXR.

Role of PXR in Hepatic Cancer: Its Influences on Liver Detoxification Capacity and Cancer Progression.

The role of nuclear receptor PXR in detoxification and clearance of xenobiotics and endobiotics is well-established. However, its projected role in hepatic cancer is rather illusive where its expression is reported altered in different cancers depending on the tissue-type and microenvironment. The expression of PXR, its target genes and their biological or clinical significance have not been examined in hepatic cancer.

Cross-talk between androgen receptor and pregnane and xenobiotic receptor reveals existence of a novel modulatory action of anti-androgenic drugs.

The androgen receptor (AR) is a member of nuclear receptor superfamily (NRs) and plays a critical role in prostate cancer development and progression. Therefore, anti-androgens that repress AR activity remain a critical mainstay for prostate cancer therapy. However, molecular mechanisms by which anti-androgens exert their therapeutic effects are not clearly elucidated and hence are a major area of scientific pursuit.