Targeted Enhancer Activation by a Subunit of the Integrator Complex.

The control of cell fate is an epigenetic process initiated by transcription factors (TFs) that recognize DNA motifs and recruit activator complexes and transcriptional machineries to chromatin. Lineage specificity is thought to be provided solely by TF-motif pairing, while the recruited activators are passive. Here, we show that INTS13, a subunit of the Integrator complex, operates as monocytic/macrophagic differentiation factor.

The Tumor Suppressor ARID1A Controls Global Transcription via Pausing of RNA Polymerase II.

AT-rich interactive domain-containing proteins 1A and 1B (ARID1A and ARID1B) are mutually exclusive subunits of the chromatin remodeler SWI/SNF. ARID1A is the most frequently mutated chromatin regulator across all cancers, and ovarian clear cell carcinoma (OCCC) carries the highest prevalence of ARID1A mutations (∼57%). Despite evidence implicating ARID1A in tumorigenesis, the mechanism remains elusive.

Gramicidin A blocks tumor growth and angiogenesis through inhibition of hypoxia-inducible factor in renal cell carcinoma.

Ionophores are hydrophobic organic molecules that disrupt cellular transmembrane potential by permeabilizing membranes to specific ions. Gramicidin A is a channel-forming ionophore that forms a hydrophilic membrane pore that permits the rapid passage of monovalent cations. Previously, we found that gramicidin A induces cellular energy stress and cell death in renal cell carcinoma (RCC) cell lines.

Epigenetic silencing of Na,K-ATPase β 1 subunit gene ATP1B1 by methylation in clear cell renal cell carcinoma.

The Na,K-ATPase or sodium pump carries out the coupled extrusion of Na(+) and uptake of K(+) across the plasma membranes of cells of most higher eukaryotes. We have shown earlier that Na,K-ATPase-β 1 (NaK-β) protein levels are highly reduced in poorly differentiated kidney carcinoma cells in culture and in patients' tumor samples. The mechanism(s) regulating the expression of NaK-β in tumor tissues has yet to be explored.

Gramicidin A induces metabolic dysfunction and energy depletion leading to cell death in renal cell carcinoma cells.

Ionophores are lipid-soluble organic molecules that disrupt cellular transmembrane potential by rendering biologic membranes permeable to specific ions. They include mobile-carriers that complex with metal cations and channel-formers that insert into the membrane to form hydrophilic pores. Although mobile-carriers possess anticancer properties, investigations on channel-formers are limited.