Cancer

Hypoxia-inducible factor 1 (HIF-1) allows cells to respond to changing levels of oxygen in the environment. HIF-1 is a heterodimeric transcription factor consisting of alpha and beta subunits. Under normal conditions HIF-1 alpha is continuously synthesized and degraded. HIF-1 alpha degradation is mediated through an oxygen-dependent degradation domain that is hydroxylated and leads to ubiquitylation and proteolysis. HIF-1 beta on the other hand is constitutively expressed and localizes to the nucleus.

The mammalian target of rapamycin (mTOR) signaling pathway allows cells to monitor environmental signals like nutrient availability and oxygen levels. mTOR is a phosphoinositide 3-kinase (PI3K)-related protein that assembles into large protein complexes (mTORC1 and mTORC2) capable of regulating cell metabolism, growth, and proliferation.

Survivin is an anti-apoptotic protein which is the smallest protein within a large family of proteins including X-linked IAP, c-IAP1 and 2, IAP-like protein-2, melanoma IAP, NAIP, and Livin. Survivin is responsible for a wide range of basic cellular functions that include the cell cycle regulation, fetal development, cell migration, and tumor progression.

Fanconi anemia (FANC) is a rare, autosomal-recessive genetic disorder that is a heterogeneous cancer susceptibility condition that manifests with a wide range of symptoms such as congenital malformations, deteriorating bone marrow failure, DNA-damage hypersensitivity, genomic instability, and increased cancer incidence. FANCD2 is a component within the protein complex that is involved in a cell's resistance to DNA cross-linking and subsequent DNA synthesis arrest that is stimulated by the insult of ionizing radiation (IR).

The Beclin 1 protein is a central regulator of autophagy in mammalian cells. Autophagy is an essential process used to maintain cellular homeostasis by degrading and recycling cellular components such as damaged or worn out organelles and macromolecules. Autophagy is also activated in response to cellular stresses such as nutrient starvation or intracellular pathogens and can protect the cell from programmed cell death.

IL-1 was originally identified and cloned as a lymphocyte mitogen and much later, was found to be comprised of two closely related but distinct proteins, interleukin 1 alpha (IL-1 alpha) and interleukin 1 beta (IL-1 beta). Both these proteins bind to the same cell surface receptor. IL-1 is primarily released from stimulated macrophages, but is also released from several other cell types. Along with other IL-1 gene family members, IL-1 beta falls within a cytokine gene cluster on chromosome 2.

The transcription factor nuclear factor kappa beta (NFkB) is highly regulated by triggers such as stress, free-radicals, UV light, and hypoxia. NFkB is one of the fastest responding transcription factors in humans. The NFKB signaling pathway is essential for cancer progression because it governs many downstream molecules that control cellular growth and development. The effects of NFkB on angiogenic pathways and cell response mechanisms to stress and damage are well established in the literature.

The D4-GDI protein is a negative regulator of the Ras-related Rho family of small molecule "molecular switch" GTPases. The Rho GTPases modify cell structure and architecture via rapid changes to the actin cytoskeleton and cell membrane. Many of these physiological processes are associated with apoptotic cell death, thus the in vivo removal of D4-GDI inhibitory block is critical for proper induction and progression of apoptosis in cells.

Chemokines play a central role in inflammation and are crucial for recruitment of immune cells to sites of infection. The chemokine-dependent activation of leukocytes occurs through binding to G-protein coupled receptors. These chemokine receptor subtypes can be divided into two major groups, CXCR and CCR.