Kuyini i-Ubiquitin futhi Kungani Kubalulekile?

-Delile

• Amaseli e-eukaryotic
• Wenzani ubiquitin?
• Kungani ubiquitin ubalulekile?
• Ngabe i-ubiquitin ingasetshenziselwa ukwelapha ezinye izimo?
• Ukuthatha

I-Ubiquitin iyi-protein encane, engu-76-amino acid, yokulawula etholwe ngonyaka we-1975. Itholakala kuwo wonke amaseli e-eukaryotic, iqondisa ukuhamba kwamaprotheni abalulekile esitokisini, ibamba iqhaza kukho konke ukuhlanganiswa kwamaprotheni amasha kanye nokubhujiswa kwamaprotheni anamaphutha.

Amaseli e-eukaryotic

Kutholakale kuwo wonke amaseli e-eukaryotic anokulandelana okufanayo kwe-amino acid, i-ubiquitin ibikade ingashintshiwe ngokuziphendukela kwemvelo. Amaseli e-eukaryotic, ngokungafani namaseli we-prokaryotic, anzima futhi aqukethe i-nucleus nezinye izindawo zomsebenzi okhethekile, ohlukaniswe ulwelwesi.

Amaseli e-eukaryotic akha izitshalo, isikhunta, nezilwane, kuyilapho amaseli e-prokaryotic akha izinto ezilula njengamagciwane.

Wenzani ubiquitin?

Amaseli emzimbeni wakho akha futhi aphule amaprotheni ngesilinganiso esisheshayo.I-Ubiquitin inamathela kuma-protein, imaka ukuthi ilahlwe. Le nqubo ibizwa ngokuthi yi-ubiquitination.

Amaprotheni amakiwe ayiswa kuma-proteasomes ukuze abhujiswe. Ngaphambi nje kokuba amaprotheni angene ku-proteasome, i-ubiquitin inqanyuliwe ukuthi isetshenziswe futhi.

Ngo-2004, umklomelo kaNobel eKhemistry wanikezwa u-Aaron Ciechanover, u-Avram Hershko, no-Irwin Rose ngokutholakala kwale nqubo, ebizwa ngokuthi yi-ubiquitin mediated degradation (proteolysis).

Kungani ubiquitin ubalulekile?

Ngokuya ngomsebenzi wayo, i-ubiquitin iye yafundelwa indima ethile ekwelashweni okungahle kuhloswe ngakho ukwelapha umdlavuza.

Odokotela bagxila kokungahambi kahle okuthile kumaseli womdlavuza okubavumela ukuthi baphile. Umgomo ukusebenzisa i-ubiquitin ukukhohlisa amaprotheni kumaseli womdlavuza ukuze kubangele ukuthi amangqamuzana omdlavuza afe.

Ucwaningo lwe-ubiquitin luholele ekwakhiweni kwama-proteasome inhibitors amathathu avunyelwe yi-Food and Drug Administration (FDA) ukwelapha abantu abane-myeloma eminingi, uhlobo lomdlavuza wegazi:

• i-bortezomib (Velcade)
• i-carfilzomib (Kyprolis)
• ixazomib (Ninlaro)

Ngabe i-ubiquitin ingasetshenziselwa ukwelapha ezinye izimo?

Ngokusho kweNational Cancer Institute, abacwaningi bacwaninga i-ubiquitin ngokuhlobana nomzimba ojwayelekile, isifo senhliziyo, umdlavuza, nezinye izifo. Bagxile ezicini eziningana ze-ubiquitin, kufaka phakathi:

• elawula ukusinda nokufa kwamangqamuzana omdlavuza
• ubuhlobo bayo nokucindezeleka
• indima yayo e-mitochondria kanye nemiphumela yesifo sayo

Ucwaningo lwamuva nje luphenye ukusetshenziswa kwe-ubiquitin emithini yeselula:

• Kuphakanyiswe ukuthi i-ubiquitin nayo iyabandakanyeka kwezinye izinqubo zamaselula, njengokusebenza kwempendulo yokuvuvukala kwe-factor factor-κB (NF-κB) nokulungiswa kokulimala kwe-DNA.
• Ukuphakanyiswa kokungasebenzi kahle kohlelo lwe-ubiquitin kungaholela ekuphazamisekeni kwe-neurodegenerative nakwezinye izifo zabantu. Lolu cwaningo lubonisa nokuthi uhlelo lwe-ubiquitin luyabandakanyeka ekwakhiweni kwezifo ezivuthayo nezizimele, njenge-arthritis ne-psoriasis.
• Kuphakanyiswe ukuthi amagciwane amaningi, kufaka phakathi umkhuhlane A (IAV), aqala ukutheleleka ngokuthatha yonke indawo.

Kodwa-ke, ngenxa yemvelo ehlukahlukene futhi eyinkimbinkimbi, izindlela ngemuva kwezenzo zomzimba kanye ne-pathophysiological yohlelo lwe-ubiquitin azikaqondakali ngokuphelele.

Ukuthatha

I-Ubiquitin idlala indima ebalulekile ekulawuleni amaprotheni ezingeni lamaselula. Odokotela bakholelwa ukuthi inamandla athembisayo ezinhlobonhlobo zokwelashwa kwamaselula okuhlosiwe.

Ucwaningo lwe-ubiquitin seluholele ekwakhiweni kwemithi yokwelashwa kwe-myeloma eminingi, uhlobo lomdlavuza wegazi. Le mithi ifaka i-bortezomib (Velcade), i-carfilzomib (i-Kyprolis), ne-ixazomib (i-Ninlaro).