Sumo if not karate!
By: Lionel Perez Valenzuela
sumoylation That is, just give me expliqueeeeeeeee!
Patience young padawan (is that today I saw "Revenge of the Sith").
The sumoylation is a modification post-translational, reversible, which aims to covalently attach one or more protein SUMO to a lysine of a target protein. The target protein is thus "tagged" and prepared for different biological processes.
is called SUMO (small ubiquitin-like modifier) \u200b\u200b a small family of proteins that modify covalently other proteins, in a similar way as does ubiquitin. Hence its name in English and the acronym.
Just as post-translational modification carried out by the ubiquitin ubiquitination is called the modification by SUMO protein is called sumoylation.
Recall that the ubiquitination is known as a sign of degradation. When the target protein is linked to ubiquitin is recognized by the 26S proteasome and then degraded.
Processes regulated by sumoylation
The SUMO protein binding to the amino acid lysine in the protein substrate is reversible and that there is a family of specific proteases called SENP (for sentrina proteases) capable of removing the SUMO protein to be labeled. SUMO alters the biochemical properties of the protein conjugate. Thereby regulating, among other processes:
- localization and intracellular traffic
- protein stability and protein-protein interaction
- transcriptional activity and protein-DNA interaction
- Signalling and nucleo-cytoplasmic transport
-
DNA replication - cell cycle regulation
- control of viral replication
- ubiquitination (recently reported)
As SUMO structure is a protein of 97 amino acids that has homology with ubiquitin. Both High and ubiquitin proteins bind to the consensus sequence. Therefore, it could be a competition between two processes. If a protein is sumoilizada ubiquitin could not be later, unless before, SUMO, was removed by a specific protease. In accordance with this reasoning, some examples show that ubiquitination and sumoylation of some proteins could be competing processes.
Definition of sumoylation
define the sumoylation as a reversible process of posttranscriptional modification, which regulates the activity of proteins covalently attached to protein SUMO.
The sumilación consists of 4 steps, similar to ubiquitination, these are:
1 - Maturation: high protein is activated by a peptidase.
2 - activation: binding to the E1 activating enzyme, ATP-dependent process
3 - Conjugation: transfer of SUMO from the E1 enzyme for conjugating protein E2 (UBC9).
4 - Ligation: The E3 enzymes are responsible for regulating the binding of SUMO to substrate proteins. Perform this process by binding both the E2 conjugating enzyme protein as substrate. This way they can stimulate the transfer of the switch.
The sumoylation and segregation of chromosomes
As noted above uses a single sumoylation conjugating enzyme called E2 (UBC9), SUMO protein to bind its substrates. Recent studies indicate that if sumoylation failure by a mutation in UBC9, the embryo viability is compromised, and that this pathway might be involved in stability and chromosome segregation.
The yeast with the mutated SUMO protein show problems in mitosis and chromosome segregation. has been established that the sumoylation is essential to recruit and retain kinetochore proteins.
These and other examples involving sumoylation as an important factor in the segregation of chromosomes and therefore cell division.
nuclear-cytoplasmic transport is regulated by sumoylation
know that Ran protein plays an important role in the transport through the nuclear pore complex (NPC) .
protein activity Ran in turn depends activator protein 1 of
This protein RanGAP1 once sumoilizada is transported to the NPC, which activates protein RAN allowing nucleo-cytoplasmic transport normal. But if the sumoylation of RanGAP1 fails, it is then transported to the NPC and alters all transport between the nucleus and cytoplasm.
Therefore sumoylation is critical for nuclear transport.
Cellular response to hypoxia and sumoylation
Hypoxia is a potentially dangerous condition where the oxygen concentration is very low and requires an adaptive response to very rapid metabolism.
hypoxic conditions can be found in tumors (as the tumor grows, cells within the tumor mass receive less oxygen and suffer necrosis) as well as in normal embryonic development.
Hypoxia triggers a major transcriptional response that promotes vascular development (new blood vessels , angiogenesis) and the formation of new red blood cells (erythropoiesis). Hypoxia also enhances glycolysis by increasing transcription of the Glut-1 genes encoding glucose transporters.
What is the master regulator gene of hypoxia?
The master regulator gene of hypoxia is hypoxia-inducible factor (HIF). HIF consists of two subunits, one of which,
If conditions are hypoxia, HIF α escapes degradation, increasing the transcription of genes responsible for the development of blood vessels like growth factor (VEGF) and increased of erythropoiesis via stimulation of the synthesis of erythropoietin (Epo).
What is the role of sumoylation in hypoxia?
Some studies report that under hypoxic conditions, HIF is sumoilizado α, this would increase stability and prevent it to be degraded via ubiquitination (see above, ubiquitination and sumoylation as antagonistic processes) . Thus, the HIF α , escapes degradation by activating the transcription of genes required to remedy the situation of hypoxia.
An important discovery of Argentine researchers
recently in the journal Cell, a team of Argentine researchers, led by Eduardo ARTZ researcher, describes the discovery of a new regulator of HIF α .
This new controller called résumé (for RWD-containing Sumoylation Enhancer), ie sumoylation enhancer containing the RWD domain (a domain-specific protein-protein interactions), also is induced by hypoxia.
So résumé is overexpressed in hypoxia, promoting the sumoylation of HIF α , increasing stability and escaping degradation. Being able to accumulate HIF α this ends in the nucleus inducing others to VEGF for angiogenesis begins and can get more oxygen to the tumor.
therefore to enhance the sumoylation of HIF α and prevent its degradation, résumé is an important factor in the survival of the tumor when it grows inside cells suffer from hypoxia. If I could be blocked résumé function, then the tumor would stop growing.
Further work in conflict with previous reports
In an excellent example of how scientific work, just a month after the publication of the discovery résumé, a U.S. team directed by Edward Yeh, provides another view of the regulation of HIF α , at least partially contrasts with the background.
In this work demonstrates the need for a protease, the SENP
During embryogenesis, one of the triggers for erythropoiesis is the physiological hypoxia that occurs during embryo growth. HIF α is again the master regulator, which induces both angiogenesis and erythropoiesis.
This group of researchers, showed that if the desumoilación fails (eg if the protease gene is mutated), there is no normal erythropoiesis the embryos die. Therefore the stabilization of HIF α not occur by sumoylation but by the desumoilación. What's more, according to Yeh's group, the sumoylation of HIF α , promotes its degradation via ubiquitination .
This research team Yeh
As we see this work shows contrasts with that reported by the team of Eduardo Artz.
But this way, with two or more different competing hypotheses, and multiple research groups involved, will surely deepen and expand our knowledge of the master regulators of cell metabolism as HIF.
