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You may include any references to papers as in: the use of JSmol in Proteopedia ^[1] or to the article describing Jmol ^[2] to the rescue.

Generalities

Function

Deubiquitinases or Deubiquitinating enzymes (DUBs) are key enzymes belonging to the vast group of proteases, allowing the degradation of ubiquitin of proteins. These enzymes are thus implicated in the regulation of protein degradation. Indeed, when a protein is going to be degraded, an enzymatic cascade will add a poly-ubiquitin fragment to the protein. This mechanism is called ubiquitination.[1] Following this step, mono or poly-ubiquitin is removed from the protein which has been degraded, by deubiquitinase. ^[3]

Families

Deubiquitinases belong to the protease family. This family is divided into five classes, according to the nature of the amino acid composition of their active site carrying out the catalysis: serine protease, cysteine proteases, acid proteases, metalloproteases, threonine proteases. DUBs belong to only two of these families: metalloproteases and cysteine proteases. Among the cysteine proteins, four subfamilies can be described according to their catalytic domains: ubiquitin-specific proteases (USP), les Ubiquitin C-terminal hydrolases (UCH), Otubain proteases (OTU) and Machado-joseph disease proteases (MJD). The deubiquitinases belonging to the family of metalloproteases all have a JAMM catalytic domain (JAB1/MPN/Mov34 metalloenzyme). ^[4]

Localization

The localization depends on the DUB we consider. However, the majority of DUBs are found in the nucleus, plasma membrane or/and in secretory and endocytic pathways. For example, in the ubiquitin-specific proteases family, the USP21 is mostly associated with microtubules and the centrosome.^[5]

Structure

^[6]

Biological role

Disease

The involvement of deubiquitinases in diseases is still poorly understood. However, it is known that they play a role in various physiological processes, particularly in the case of cancers. ^[7] In fact, DUBs have a role in the mechanism involved in histone modification and so have influence on tumor development and progression. For instance, in gastric cancer, DUBs are regulated upwards and DUBs are related to tumor size. ^[8]

Structural highlights

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