Cancer

Human hepatocytes express important transport proteins that are responsible for the uptake and removal of organic anions from the blood. These proteins are members of the organic anion-transporting polypeptide (OATP) family and are essential for proper liver function. OATPs are encoded by the SLC21 gene family and contain 12 transmembrane alpha-helices and are primarily expressed in the liver. The OATP family transports endogenous substrates like bile salts and steroid hormones as well as exogenous molecules like anticancer drugs and imaging agents.

c-Myc is a protein of the Myc family of transcription factors (c-Myc, B-Myc, L-Myc, N-Myc, and s-Myc) encoded by the MYC proto-oncogene. c-Myc was first discovered as the cellular homolog of the retroviral v-Myc oncogene. c-Myc is a transcription factor for genes involved in cell growth, proliferation, differentiation, and apoptosis. c-Myc contains a basic helix-loop-helix domain and a leucine zipper domain that allow for its heterodimerization with its binding partner Max. Myc/Max complexes are able to activate genes via the Myc transactivation domain (1).

Matrix metalloproteinases (MMPs) are responsible for the degradation of extracellular matrix proteins. MMPs are essential for tissue remodeling during normal processes such as embryonic development as well as pathological conditions such as arthritis and tumor metastasis. MMP3, a member of the stromelysin family, has broad specificity for proteins such as collagens, fibronectin, proteoglycans, and elastin making it an important player in extracellular matrix remodeling. These activities are especially important during tumorigenesis by enhancing epithelial to mesenchymal transition.

The vertebrate fibroblast growth factor receptor (FGFR) family is an important group of proteins involved in embryonic development and the growth and proliferation of adult cells. Mutations in FGFR proteins can lead to pathologies including bone or limb defects and various forms of cancer. FGFR proteins are receptor tyrosine kinases that, upon ligand binding, dimerize and signal through the MAPK and PLCγ pathways.

Integrins are a family of transmembrane proteins involved in diverse processes including cell adhesion, signal transduction, cell migration, and differentiation. They exist as heterodimers consisting of noncovalently linked alpha and beta subunits. Integrin complexes span the plasma membrane and link the cytoskeleton with the extracellular matrix. In mammals there are 18 alpha and 8 beta subunits that can assemble into 24 distinct integrin heterodimers with alternative splicing adding even more diversity.

The transforming growth factor-β (TGF-beta) family consists of a wide variety of signaling proteins with roles in development. TGF-beta signaling controls growth, differentiation, and immune responses and is often misregulated in cancer. TGF-beta 1 is the most widely expressed and abundant isoform of the TGF-beta family. TGF-beta proteins signal through two classes of receptors: type I (TβRI) and type II (TβRI). These receptor proteins are serine threonine kinases found at the cell surface.

Noxa is a BH3-only protein involved in regulating cell death decisions. Noxa is a primary p53-response gene and is upregulated in response to p53 overexpression or DNA damage. Noxa can also be induced by alternative mechanisms including through a hypoxia-response element found in its promoter. Noxa localizes to mitochondria where it binds to Mcl1, an anti-apoptotic Bcl2 family member.

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.

Cluster of differentiation 74 (CD74) is an important integral membrane protein that serves as a chaperone for MHC class II molecules. CD74, also known as the invariant chain or Ii, is needed for the proper folding and trafficking of MHC class II in antigen presenting cells. CD74 serves as a scaffold for MHC class II assembly. During assembly CD74 blocks the peptide binding cleft of MHC class II to prevent binding of antigenic peptides.

Mucin 1 (Muc1) is a heavily glycosylated protein that coats mucosal epithelial cells of the lungs, intestines, and other organs. Muc1 is thought to protect cells by binding to pathogens and responding to infections. During trafficking to the plasma membrane Muc1 is proteolytically cleaved in the endoplasmic reticulum to form a stable heterodimeric complex of two fragments. The smaller C-terminal region contains the cytoplasmic tail and transmembrane domain and is non-covalently bound to the larger glycosylated extracellular domain.