mdm2 is an E3 ubiquitin ligase that recognizes the N-terminal activation domain (TAD) of the p53 transcription factor. Mdm2 is a p53 responsive gene—that is, its transcription requires p53. Thus when p53 is high, Mdm2 is also high. One of the functions of mdm2 is to bind to p53, leading to its ubiquitination, export out of the nucleus and subsequent degradation of p53 by the proteasome. (See Proteasome and Ubiquitin). In this manner, Mdm2 and p53 are the members of a negative feedback control loop that keeps the level of p53 low. This loop can be interfered with by kinases and genes like p14arf when p53 activation signals are high. A Ubiquitin ligase is a protein which covalently attaches ubiquitin to a lysine residue on a target protein. ... The N-terminal end refers to the extremity of a protein or polypeptide terminated by an amino acid with a free amine group (NH2). ... // Background Ubiquitylation, also termed ubiquitination, refers to the process particular to eukaryotes whereby a protein is post-translationally modified by covalent attachment of a small protein. ... Nucleus usually refers to the center of something, but can mean: In science: Atomic nucleus, the collection of protons and neutrons in the center of an atom that carries the bulk of the atoms mass and positive charge Cell nucleus, the membrane-bound subcellular organelle found in eukaryotes, visible... A proteasome is a barrel-shaped multi-protein complex that can digest other proteins into short polypeptides and amino acids in an ATP-driven reaction. ... Ubiquitin is a small regulatory protein that is ubiquitous in eukaryotes. ... In biochemistry, a kinase is a type of enzyme that transfers phosphate groups from, for example, ATP to a specified substrate or target; the process is termed phosphorylation. Typically, the target is activated or energized by being phosphorylated. ... p14ARF is a alternate reading frame (ARF) product of the INK4 gene. ...