since
July 10, 2000
PROTEASOME F.A.Q.
It was first discovered by SherwinWilk and Marian Orlowski at the Departmentof Pharmacology, Mount Sinai School of Medicine (NY,NY) in 1980 asa neutral endopeptidase from bovine pituitaries,displaying multicatalytic activities. Arrigo et al. in 1988 showed thatthis protease (called MPC or multicatalytic protease complex) is identicalwith a particle known as the prosome and discovered by the group of KlausScherrer. It was in this paper, that Arrigo proposed the name proteasome.
Is proteasome an organelle?
Well, in the classic sense of amembrane bound compartment it is not, however in the same sense as ribosomesare called organelles, proteasomes also deserve that name.
How does it look like?
while
on electron microscopy like that:
The electron micrograph depicts the 20 S proteasomeassociated with two additional 19 S complexes (also called PA700 activators)to form a structure known as 26 S proteasome. While the 20 S proteasomedegrades only short peptides and is unable to degrade native proteins,the 26 S proteasome degrades native proteins linked with polyubiquitinchains with the use of ATP. The 20 S proteasome is the core of this structureand is arranged of four stacked rings, two outer alpha rings and two innerbeta rings, each ring consistent of 7 subunits. While in archeabacteriaeach ring type is made of a identical subunits, eukaryotes have seven differentalpha and seven different beta subunits. This complexity even increasesin vertebrates when three additional beta subunits are found, being inducedby gamma-interferon and implicated in antigen presentation.
Why is proteasome so important?
The ubiquitin/proteasome pathway is responsiblefor the degradation of the vast majority of cellular proteins, includingnot only short-lived regulatory proteins (like cyclins, cyclin inhibitors,oncogene products etc.) but also the bulk of long-lived cellular proteins.The 19 S cap complexes contain subunits with ATP-ase activity and subunitsable to bind and recognize polyubiquitin chains as well as putative unfoldasesor inverse chaperonins which most probably unfold protein chains and translocatethem through the central channel of the core 20 S proteasome to the innerchamber, where catalytically active threonines of at least three differentbeta subunits reside. Biochemical studies of the 20 S proteasome revealedat least three different proteolytic activities designed chymotrypsin-like(ChTL), trypsin-like (TL) and peptidylglutamylpeptide hydrolyzing (PGPH)and two minor activities - branched amino acids preferring and small neutralamino acids preferring. From all those activities ChTL activity seems tobe most important, since the use of specific inhibitors of this activityleads to the rapid accumulation of ubiquitin-protein conjugates, cell vacuolization,cell cycle block and apoptosis.
What is this "ubiquitin conjugating system"?
Have a look on this drawing:
U - represents free ubiquitins and ubiquitin moietiescovalently attached to the substrate. Ubiquitin attaches to the epsilonamino group of lysines in the substates as well as to Lys in other ubiquitinmolecules.
To learn more what is ubiquitin and how it isselectively conjugated to proteins which are subsequently degraded by theproteasome go to this excellent web page http://www.nottingham.ac.uk/~mbzmail/students/ub/ubindex.html
Yes! You are very welcome! Just write me whatlink or information you would like to have included! Advertisement fromcompanies offereing items for proteasome-related research are welcome!Announcements of meetings and conferences about this area are welcome aswell.
Visit us soon - more will follow!The PROTEASOME awaits you!
ViewMy
Guestbook
Backto the Department of HistologyBackto Cezary Wojcik's Home Page |