Chii chinonzi Ubiquitin uye Nei Chakakosha?

Zvemukati

• Eukaryotic masero
• Chii chinonzi ubiquitin?
• Nei ubiquitin yakakosha?
• Ko ubiquitin inogona kushandiswa kurapa mamwe mamiriro?
• Kutora

Ubiquitin idiki, 76-amino acid, inoronga mapuroteni akawanikwa muna 1975. Iripo mumasero ese eukaryotic, ichitungamira kufamba kwemapuroteni akakosha muchitokisi, kutora chikamu mune zvese kuwanda kwemapuroteni matsva uye kuparadzwa kwemapuroteni asina kukwana.

Eukaryotic masero

Inowanikwa mune ese eukaryotic maseru ane akafanana amino acid akateedzana, ubiquitin anga asingachinji nekushanduka. Masero eEukaryotic, zvinopesana nemasero eprokaryotic, akaomarara uye ane nucleus nedzimwe nzvimbo dzehunyanzvi basa, rakaparadzaniswa nemakemikari.

Eukaryotic masero anogadzira zvirimwa, fungi, uye mhuka, nepo prokaryotic maseru achiumba zvipuka zvakapusa kunge mabhakitiriya.

Chii chinonzi ubiquitin?

Maseru mumuviri wako anovaka uye kuputsa mapuroteni nekukurumidza. Ubiquitin inosungira kumapuroteni, achiaisa iwo ekurasa. Maitiro aya anonzi ubiquitination.

Tagged mapuroteni anoendeswa kuma proteasomes kuti aparadzwe. Nguva pfupi puroteni isati yapinda muproteasome, ubiquitin inodamburwa kuti ishandiswe zvakare.

Muna 2004, mubayiro weNobel muKemistry wakapihwa Aaron Ciechanover, Avram Hershko, naIrwin Rose pakuwanikwa kwechirongwa ichi, chinonzi ubiquitin mediated degradation (proteolysis).

Nei ubiquitin yakakosha?

Zvichienderana nebasa rayo, ubiquitin yakadzidzwa nezvechinzvimbo mune zvinogona kurapwa tarisiro yekurapa cancer.

Vanachiremba vanotarisa pane zvisina kufanira mumasero ekenza anovabvumira kurarama. Chinangwa ndechekushandisa ubiquitin kushandisa protein mumaseru ekenza kuti kenza yesero ife.

Kudzidza kweubiquitin kwakatungamira mukuvandudzwa kwematatu eproteasome inhibitors anotenderwa neKudya neDrug Administration (FDA) kurapa vanhu vane myeloma yakawanda, fomu rekenza yeropa:

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

Ko ubiquitin inogona kushandiswa kurapa mamwe mamiriro?

Sekureva kweNational Cancer Institute, vatsvagiri vari kudzidza ubiquitin muhukama neyakajairika physiology, chirwere chemoyo, gomarara, uye zvimwe zvinetso. Ivo vari kutarisa kune akati wandei mativi eubiquitin, kusanganisira:

• kugadzirisa kupona uye kufa kwemasero ekenza
• hukama hwayo nekushushikana
• basa rayo pa mitochondria uye nezvayo chirwere

Ongororo dzinoverengeka dzichangobva kuitwa dzakatsvaga kushandiswa kweubiquitin mumushonga wemagetsi:

• A yakaratidza kuti ubiquitin inobatanidzwawo mune mamwe maseru maitiro, sekumisikidza yenyukireya factor-κB (NF-κB) yekupindura mhinduro uye DNA kukuvara kugadzirisa.
• Iyo yakaratidza kuti kusagadzikana kweiyo ubiquitin system kunogona kutungamira kune neurodegenerative kusagadzikana uye zvimwe zvirwere zvevanhu. Ichi chidzidzo zvakare chinoratidza kuti iyo ubiquitin system inobatanidzwa mukuvandudza kweanopisa uye autoimmune hosha, senge arthritis uye psoriasis.
• A yakaratidza kuti mazhinji mavairasi, kusanganisira furuwenza A (IAV), inogadzira hutachiona nekutora ubiquitination.

Nekudaro, nekuda kwehunhu hwayo hwakasiyana uye hwakaomarara, maficha ari kumashure kwezviito zvemuviri uye zvepathophysiological yeiyo ubiquitin system haisati yanyatsonzwisiswa.

Kutora

Ubiquitin inoita basa rakakosha mukugadzirisa mapuroteni pasero renhare. Vanachiremba vanotenda kuti ine anovimbisa mukana weakasiyana eanotarisirwa maseru ekurapa ekurapa.

Kudzidza kweubiquitin kwakatotungamira mukugadzirwa kwemishonga yekurapa kweakawanda myeloma, chimiro chekenza yeropa. Iyi mishonga inosanganisira bortezomib (Velcade), carfilzomib (Kyprolis), uye ixazomib (Ninlaro).