Is Mdm2 a ubiquitin ligase?
Mdm2 is an important negative regulator of the p53 tumor suppressor. Mdm2 protein functions both as an E3 ubiquitin ligase that recognizes the N-terminal trans-activation domain (TAD) of the p53 tumor suppressor and as an inhibitor of p53 transcriptional activation.
What is Parkin Parkinson’s disease?
Parkin (Parkinson juvenile disease protein 2) is a ~52 kDa (426 amino acid) enzyme protein, encoded by PARK2 gene and located on the 6q chromosome. It plays an important role in the ubiquitin-proteasome system and acts as a regulator of protein breakdown.
How many E1 enzymes are there in humans?
To date, there are two E1 enzymes, approximately 40 E2s, and approximately 600-1000 E3s known to be encoded by the human genome, which collectively coordinate the ubiquitination of thousands of substrates [10] [11] [12][13].
What are HECT-type E3 ubiquitin ligases?
The HECT-type E3 ubiquitin ligases constitute a small subfamily of E3s (28 enzymes in human) that have intrinsic enzymatic activity. Members of the subfamily of HECT-type E3s are frequently deregulated in human cancers.
What is HECT E3 ligase dysfunction?
Several HECT E3 ligases have been implicated in various types of cancers, neurodegenerative diseases and viral infections. Many of these diseases caused by HECT E3 ubiquitin ligase dysfunction have been genetically linked or caused by changes in protein expression, stability and/or ubiquitylation activity.
What is E3 ubiquitin ligase Itch deficiency?
The E3 ubiquitin ligase Itch deficiency promotes antigen-driven B-cell responses in mice. Ubiquitination of interleukin-1alpha is associated with increased pro-inflammatory polarization of murine macrophages deficient in the E3 ligase ITCH.
Do different HECT domain ubiquitin ligases employ distinct mechanisms of polyubiquitin synthesis?
Different HECT domain ubiquitin ligases employ distinct mechanisms of polyubiquitin chain synthesis. Embo J. 24, 4324–4333. doi: 10.1038/sj.emboj.7600895