Erad

Erad or ERAD may refer to:

See also

Jared Lee Loughner

Jared Lee Loughner (/ˈlɒfnər/; born September 10, 1988) is an American citizen who pleaded guilty to 19 charges of murder and attempted murder in connection with the January 8, 2011 Tucson shooting, in which he shot and severely injured U.S. Representative Gabrielle Giffords, his target, and killed 6 people, including Chief U.S. District Court Judge John Roll, as well as a 9-year-old bystander Christina-Taylor Green. Loughner shot and injured 13 other people, and one man was injured while subduing him.

Acquaintances said that Loughner's personality had changed markedly in the years prior to the shooting, a period when he was also abusing alcohol and drugs. He had been suspended from Pima Community College in September 2010 because of his bizarre behavior and disruptions in classes and the library. After his arrest, two medical evaluations diagnosed him as paranoid schizophrenic and incompetent to stand trial. He was medicated while in jail as part of his treatment. He was again judged incompetent in May 2012.

Endoplasmic-reticulum-associated protein degradation

Endoplasmic-reticulum-associated protein degradation (ERAD) designates a cellular pathway which targets misfolded proteins of the endoplasmic reticulum for ubiquitination and subsequent degradation by a protein-degrading complex, called the proteasome.

Mechanism

The process of ERAD can be divided into three steps:

Recognition of misfolded or mutated proteins in the endoplasmic reticulum

The recognition of misfolded or mutated proteins depends on the detection of substructures within proteins such as exposed hydrophobic regions, unpaired cysteine residues and immature glycans.

In mammalian cells for example, there exists a mechanism called glycan processing. In this mechanism, the lectin-type chaperones calnexin/calreticulin (CNX/CRT) provide immature glycoproteins the opportunity to reach their native conformation. They can do this by way of reglucosylating these glycoproteins by an enzyme called UDP-glucose-glycoprotein glucosyltransferase. Terminally misfolded proteins, however, must be extracted from CNX/CRT. This is carried out by EDEM (ER degradation-enhancing α-mannosidase-like protein) and ER mannosidase I. This mannosidase removes one mannose residue from the glycoprotein and the latter is recognized by EDEM. Eventually EDEM will target the misfolded glycoproteins for degradation.