Yintoni i-Ubiquitin kwaye kutheni ibalulekile?

Umxholo

• Iiseli ze-Eukaryotic
• Wenza ntoni ubiquitin?
• Kutheni le nto ubhiquitin ibalulekile?
• Ngaba i-ubiquitin inokusetyenziselwa ukunyanga ezinye iimeko?
• Ukuthatha

I-Ubiquitin yincinci, i-76-amino acid, iprotein yolawulo eyafunyanwa ngo-1975. Ikho kuzo zonke iiseli ze-eukaryotic, ikhokela ukuhamba kweeproteni ezibalulekileyo kwiseli, ithatha inxaxheba kuzo zombini ukuhlanganiswa kweeproteni ezintsha kunye nokutshabalalisa iiproteni ezineziphene.

Iiseli ze-Eukaryotic

Ifunyenwe kuzo zonke iiseli ze-eukaryotic ezinokulandelelana okufanayo kwe-amino acid, i-ubiquitin ayitshintshanga ngenguquko. Iiseli ze-Eukaryotic, ngokuchaseneyo neeseli zeprokaryotic, zintsonkothile kwaye ziqulathe i-nucleus kunye nezinye iindawo zomsebenzi okhethekileyo, ezahlulwe ngenwebu.

Iiseli ze-eukaryotic zenza izityalo, ukungunda kunye nezilwanyana, ngelixa iiseli zeprokaryotic zenza izinto ezilula ezifana neebhaktiriya.

Wenza ntoni ubiquitin?

Iiseli zomzimba wakho ziyakha kwaye ziqhekeze iiproteni ngesantya esikhawulezayo. I-Ubiquitin incamathela kwiiproteni, ukuzithenga ukuze zilahlwe. Le nkqubo ibizwa ngokuba yi-ubiquitination.

Iiproteni ezimakiweyo zithathwa kwiiproteasomes ukuze zitshatyalaliswe. Ngaphambi nje kokuba iprotein ingene kwiproteasome, i-ubiquitin iyanqanyulwa ukuze iphinde isetyenziswe.

Ngo-2004, imbasa kaNobel eKhemistry yanikwa uAaron Ciechanover, uAvram Hershko, kunye no-Irwin Rose ngokufumanisa le nkqubo, ibizwa ngokuba yi-ubiquitin mediated degradation (proteolysis).

Kutheni le nto ubhiquitin ibalulekile?

Ngokusekwe ekusebenzeni kwayo, i-ubiquitin ifundelwe ngendima kunyango ekujolise kulo ukunyanga umhlaza.

Oogqirha bagxila kwizitenxo ezithile kwiiseli zomhlaza ezibavumela ukuba baphile. Injongo kukusebenzisa i-ubiquitin ukusebenzisa iproteni ekwiiseli zomhlaza ukwenza ukuba iseli yomhlaza ife.

Uphononongo lwe-ubiquitin lukhokelele kuphuhliso lwee-inhibitors ezintathu ze-proteasome ezivunywe yi-Food and Drug Administration (i-FDA) ukunyanga abantu abane-myeloma, uhlobo lomhlaza wegazi:

• ibortezomib (Velcade)
• icarfilzomib (iKyprolis)
• ixazomib (Ninlaro)

Ngaba i-ubiquitin inokusetyenziselwa ukunyanga ezinye iimeko?

Ngokwe-National Cancer Institute, abaphandi bafunda i-ubiquitin ngokunxulumene nomzimba oqhelekileyo, isifo sentliziyo, umhlaza kunye nezinye iingxaki. Bajolise kwimicimbi eliqela ye-ubiquitin, kubandakanya:

• Ukulawula ukusinda kunye nokufa kweeseli zomhlaza
• ubudlelwane bayo noxinzelelo
• Indima yayo kwi-mitochondria kunye nesifo sayo

Izifundo ezininzi zamva nje ziphande ukusetyenziswa kwe-ubiquitin kunyango lweselula:

• Isiphakamiso sokuba i-ubiquitin ikwabandakanyeka kwezinye iinkqubo zeselfowuni, ezinje ngokusebenza kwenyukliya-κB (NF-κB) impendulo yokuvuvukala kunye nokulungiswa komonakalo we-DNA.
• Isiphakamiso sokuba ukungasebenzi kwenkqubo ye-ubiquitin kunokukhokelela kuphazamiseko lwe-neurodegenerative kunye nezinye izifo zabantu. Olu pho nonongo lubonisa ukuba inkqubo ye-ubiquitin iyabandakanyeka ekuphuhliseni izifo ezivuthayo kunye nezifo ezizimele, ezifana ne-arthritis kunye ne-psoriasis.
• Kucetyiswa ukuba uninzi lweentsholongwane, kubandakanya umkhuhlane A (IAV), luseke usulelo ngokuthatha ubiquitination.

Nangona kunjalo, ngenxa yohlobo lwayo olwahlukeneyo nolunzima, iindlela ezisemva kokusebenza komzimba kunye ne-pathophysiological yenkqubo ye-ubiquitin ayikaqondwa ngokupheleleyo.

Ukuthatha

I-Ubiquitin idlala indima ebalulekileyo kulawulo lweeproteni kwinqanaba leselula. Oogqirha bakholelwa ekubeni inezithembiso ezinokubakho kwizonyango ezahlukeneyo ekujolise kuzo zonyango.

Isifundo se-ubiquitin sele sikhokelele kuphuhliso lwamayeza kunyango lwe-myeloma, uhlobo lomhlaza wegazi. La mayeza aquka i-bortezomib (Velcade), i-carfilzomib (iKyprolis), kunye ne-ixazomib (Ninlaro).