SUMO protein
SUMOylation is a post-translational modification involved in various cellular processes, such as nuclear-cytosolic transport, transcriptional regulation, apoptosis, protein stability, response to stress, and progression through the cell cycle.
[1] In human proteins, there are over 53,000 SUMO binding sites, making it a substantial component of fundamental biology.
Typically, only a small fraction of a given protein is SUMOylated and this modification is rapidly reversed by the action of deSUMOylating enzymes.
SUMOylation of target proteins has been shown to cause a number of different outcomes including altered localization and binding partners.
As a result, SUMO-4 isn't processed and conjugated under normal conditions, but is used for modification of proteins under stress-conditions like starvation.
The exact length and mass varies between SUMO family members and depends on which organism the protein comes from.
Currently available prediction programs are: SUMO attachment to its target is similar to that of ubiquitin (as it is for the other ubiquitin-like proteins such as NEDD 8).
It is thought that the E3 ligase promotes the efficiency of SUMOylation and in some cases has been shown to direct SUMO conjugation onto non-consensus motifs.
[21] Recent evidence has shown that PIAS-gamma is required for the SUMOylation of the transcription factor yy1 but it is independent of the zinc-RING finger (identified as the functional domain of the E3 ligases).
In cell cycle regulation, the base case is that SUMO ligation is constantly taking place, leading to polySUMOylation of eligible target proteins.
This is countered by the SUMO protease Ulp2 which cleaves polySUMO groups, leaving the protein in a monoSUMOylated state.
Cdc5 is countered by the Rts1-PP2A phosphatase, which maintains the active state of the Ulp2 SUMO protease by removing the phosphate group added by Cdc5 kinase.
[23] As studied with budding yeast, in the case of Tof2-Cdc14, Cdc14 release from the nucleolus allows the Mitotic Exit Network to commence, but it is regulated by the binding of Tof2, a protein subject to SUMOylation.
[25] The importance of these studies in models such as yeast lies in their potential to inform scientists in the research and development of precise biomedical interventions that can translate to the improvement of human health in an array of clinical aspects.
[30] The critical nature of p53 cannot be overstated: in fact, if a human carries only one non-functioning copy of p53, it results in a deadly cancer prognosis known as Li-Fraumeni syndrome.
[32] The fallout from deSUMOylation of HIF-1α includes promotion of MMPs which are understood to contribute to the progression of EMT, a hallmark of cancer.
The stimulus is transduced by the activation of a serine/threonine kinsase called p90RSK, which phosphorylates the human SUMO protease SENP2 at the throenine amino acid residue 368.
Nuclear export of SENP2 additionally downregulates endothelial nitric oxide synthase, eNOS while it upregulates inflammatory adhesion molecules.
To say SUMOylation itself is bad or good regarding this or any other class of disease is to overlook the role of the multiple proteins in question.
Other accumulating proteins which threaten neurodegenerative disorders include α-synuclein (associated with Parkinson's) and Amyloid β (associated with Alzheimer's), and if acted upon early enough, disease could perhaps be better mitigated.
[39] Recombinant proteins expressed in E. coli may fail to fold properly, instead forming aggregates and precipitating as inclusion bodies.
[42] This insolubility may be due to the presence of codons read inefficiently by E. coli, differences in eukaryotic and prokaryotic ribosomes, or lack of appropriate molecular chaperones for proper protein folding.
