Tumor

The protein ATF6 is a constitutively expressed transcription factor that is a key mediator of the unfolded protein response (UPR) that allows mammalian cells to maintain cellular homeostasis under conditions of environmental and physiological stress. ATF6 is endoplasmic reticulum (ER) membrane-anchored in its inactive form, and under certain stress conditions, translocates to the Golgi where it is processed into its active form through action of the S1P and S2P proteases.

The CIP2A protein was originally identified as p90, a cytoplasmic auto-antigen from the serum of a cancer patient. It was later found to inhibit protein phosphatase 2A (PP2A) activity as well as interact with c-myc. CIP2A's inhibitory activity blocks c-myc phosphorylation and its subsequent proteolytic degradation, producing a stable c-myc that promotes aberrant cell growth and transformation. In addition to its role in c-Myc stabilization, CIP2A promotes anchorage-independent cell growth and in vivo tumor formation.

LOX is a copper-dependent amine oxidase enzyme that executes post-translational oxidative deamination on peptidyl lysine residues in precursors of fibrous collagen and elastin. LOX is secreted into the extracellular environment in an inactive form, where it is processed into an active form. Its activity is crucial for maintaining both the tensile and elastic properties of connective tissue residing within skeletal, pulmonary, and cardiovascular systems.

LAMP2 belongs to the family of membrane glycoproteins who confer selectins with carbohydrate ligands. LAMP2 has been implicated in tumor cell metastasis, as well as overall protection, maintenance, and adhesion of the lysosome. It appears that LAMP2 may protect the lysosomal membrane from autophagy, as well as maintain the required acidic environment necessary for proper function.  LAMP2 is a single-pass type I membrane protein that shuttles between endosomes, lysosomes, and the plasma membrane.

The protein encoded by SNF5 is a component of the chromatin-remodeling protein complex responsible for relieving repressive chromatin structures by allowing the transcriptional machinery to access targets more effectively. SNF5 has been found to be a tumor suppressor, and mutations within it are associated with some malignant tumors. Two transcript variants encoding different isoforms exist. Scurr’s group published interesting findings on effector proteins in senescence in Cell¹.

p73 has been identified as a long-lost cousin of the p53 tumor suppressor protein. It has high homology with both p53 and with p63, a gene implicated in the maintenance of epithelial stem cells. The presence of significant homology between the DNA-binding domains of p53, p63, and p73 suggest that they have overlapping functions. Targeted disruption of p73 leads to defects hippocampal dysgenesis, hydrocephalus, chronic inflammation, and infections.

MMP2 is a peptidase enzyme that belongs to the large family of matrix metalloproteinases (MMPs) which degrade the extracellular matrix (ECM) with different substrate specificities. Aberrant and unregulated expression of MMPs via deregulation of key negative check controls is strongly associated with increased tumor invasiveness, metastasis potential, and angiogenesis. This uncontrolled behavior is in direct contrast to the tightly controlled physiological systems of embryonic development, tissue remodeling, and rebuilding.

Cell death via apoptosis is a fundamental cellular function triggered by the cell death receptor family and their ligands which signal through downstream adaptor molecules and the caspase protease family. All caspases exist in a precursor form composed of a prodomain, and large and small catalytic subunits. Caspases require a cleavage adjacent to an aspartate to liberate one large and one small subunit, which can then associate into an a2b2 tetramer.

Platelet endothelial cell adhesion molecule 1 (PECAM1), also known as cluster of differentiation 31 (CD31), is a cell-surface glycoprotein expressed on platelets, monocytes, neutrophils, some types of T-cells and NK (natural killer) cells. It makes up a large portion of the endothelial cell intercellular junctions. CD31/PECAM1 is a member of the immunoglobulin superfamily and plays many different roles involving leukocyte migration under most inflammatory conditions, angiogenesis, integrin activation, atherosclerosis and thrombopoiesis.

Akt1 is a serine/threonine-specific protein kinase involved in many cellular signaling pathways. The major function of this kinase is to mediate cell survival, but it also plays key roles in various other cellular functions such as glycogen synthesis and cell growth. Akt1 acts as a transducer for growth factor receptors that modulate phosphatidylinositol 3-kinase (PI3K) activity. Akt is believed to be a factor in cancer as the tumor suppressor phosphatase and tensin homolog (PTEN) was found to antagonize both PI-3 kinase and Akt kinase activity.