STAT3

By Jamshed Arslan, Pharm. D., PhD.

Signal transducer and activator of transcription 3 (STAT3) is an important oncogenic transcriptional factor that mediates tumor induced immune suppression.  Specifically, STAT3 transmits signals from cytokines and growth factor receptors in the plasma membrane (PM) to the nucleus, where they alter gene transcription.  Because of this transcriptional regulatory role, STAT3 also plays a part in regulating transcription of many critical genes that are involved in apoptosis, cell differentiation, immune response, tumor formation and more.  Using a

Krüppel-like factors (KLFs) are evolutionarily conserved zinc finger transcription factors that play a role in cell differentiation, proliferation, and pluripotency.

Human leukocyte antigen G (HLA G) is a major histocompatibility complex (MHC) class I molecule that is primarily expressed in the placenta and is essential for the immune tolerance of the fetus during pregnancy. Unlike many HLA genes, HLA G has relatively few variants and is alternatively spliced into seven different isoforms. Of these isoforms four are membrane-bound while three are predicted to be soluble. Both the membrane-bound and soluble form of HLA G can induce immune tolerance by binding to inhibitory receptors on various immune cells including macrophages and monocytes.

Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric transcription factor consisting of alpha and beta subunits. The levels of functional HIF-1 in the cell depends on the level of oxygen allowing cells to respond to hypoxic conditions. HIF-1α is a ubiquitously expressed protein containing an oxygen-dependent degradation domain that under normal conditions regulates its constant degradation. HIF-1 beta, on the other hand, is a stable constitutively expressed protein that localizes to the nucleus.

Toll-like receptor 4 (TLR4) belongs to the family of Toll-like receptors (TLR), and plays a main role in pathogen recognition and innate immunity system activation. The TLR family members are highly conserved proteins that all contain a high degree of structural and functional homology in organisms from Drosophila all the way up to humans. TLRs regulate the cellular cytokine production required for efficient innate immunity development through their recognition of pathogen-associated molecular patterns (PAMPs) expressed across a wide range of ligands, including infectious agents.

Thymoquinone (2-isopropyl-5-methyl-1,4-benzoquinone, or TQ) is derived from the seeds of the black cumin plant Nigella sativa. It has been reported to have a number of beneficial properties including anti-oxidative, anti-inflammatory and anti-tumorigenic activities and, like many other natural products, derivatives and analogues of thymoquinone are being synthesised in an effort to increase its therapeutic potential.

Survivin (BRIC5) is an inhibitor of apoptosis that also promotes cellular adaptation under stressful conditions and helps to regulate cell division. Recently, an antibody study by Dr. H Wang et al. at Brown University [PMID: 20826784] found that Survivin is acetylated at lysine residue 129, thereby affecting its subsequent subcellular localization.