ʻO ka lāʻau lapaʻauthalidomideUa hoʻomanaʻo ʻia i ka makahiki 1960 no ka mea ua hoʻopilikia nui ʻia i nā pēpē hou, akā i ka manawa like ua hoʻohana nui ʻia e mālama i nā maʻi sclerosis a me nā maʻi maʻi koko ʻē aʻe, a hiki iā ia, me kona mau ʻohana kemika, ke hoʻoikaika i ka luku ʻana i nā ʻāpana ʻelua o nā protein kikoʻī he lālā o ia. he ʻohana o nā polokina maʻamau "ʻaʻohe lāʻau" (nā mea kākau) i loaʻa kahi ʻano molekala kikoʻī, ka C2H2 zinc finger motif.

Ma kahi noiʻi hou i paʻi ʻia ma ka puke moʻolelo honua ʻepekema, ʻike nā ʻepekema mai ka MIT Boulder Institute a me nā ʻoihana ʻē aʻe e hiki i ka thalidomide a me nā lāʻau lapaʻau pili ke hāʻawi i kahi hoʻomaka no nā mea noiʻi e hoʻomohala i kahi ʻano hui anti-cancer hou i manaʻo ʻia e hoʻopaʻa ʻia ma kahi o 800. nā mea unuhi i kaʻana like. Hoʻopili nā mea unuhi i ka DNA a hoʻonohonoho i ka hōʻike ʻana o nā genes he nui, i kikoʻī pinepine ʻia i nā ʻano cell a i ʻole nā ​​kikoʻī; pili kēia mau protein i nā maʻi maʻi he nui ke hele hewa lākou, akā ua ʻike ka poʻe noiʻi he paʻakikī paha ka hoʻopaʻa ʻana iā lākou no ka hoʻomohala ʻana i ka lāʻau lapaʻau no ka mea ʻaʻole pinepine nā mea transcription i nā pūnaewele kahi e pili pono ai nā molekala lāʻau me lākou.

Hiki iā Thalidomide a me kona mau ʻohana kemika pomalidomide a me lenalidomide ke hoʻouka pololei i kā lākou mau pahuhopu ma ke kau inoa ʻana i kahi pūmua i kapa ʻia ʻo cereblon - ʻelua kumu transcription i loaʻa iā C2H2 ZF: IKZF1 a me IKZF3. ʻO Cereblon kahi mole mole i kapa ʻia ʻo E3 ubiquitin ligase a hiki ke hoʻopaʻa inoa i nā protein kikoʻī no ka hoʻohaʻahaʻa ʻana e ka ʻōnaehana cellular circulatory. I ka loaʻa ʻole o ka thalidomide a me kona ʻohana, ʻaʻole ʻike ka cereblon iā IKZF1 a me IKZF3; i ko lākou alo, hoʻolaha ia i ka ʻike ʻana i kēia mau mea transcription a me kā lākou lepili no ka hana ʻana.

He kuleana hou nokeiakahikolāʻau lapaʻau

Hiki i ka genome kanaka ke hoʻopili i nā mea transcription 800, e like me IKZF1 a me IKZF3, hiki ke ʻae i kekahi mau hoʻololi ʻana i ke kumu C2H2 ZF; ʻO ka ʻike ʻana i nā mea kikoʻī e hiki ke kōkua i ka hoʻomohala ʻana i ka lāʻau lapaʻau hiki ke kōkua i ka poʻe noiʻi e ʻike inā hiki ke loaʻa nā mea kākau like ʻē aʻe i nā lāʻau lapaʻau e like me thalidomide. Inā loaʻa kekahi lāʻau lapaʻau like thalidomide, hiki i nā mea noiʻi ke hoʻoholo i nā waiwai C2H2 ZF pololei i ʻike ʻia e ka cereblon protein, a laila nānā ʻia no ka hikithalidomide, pomalidomide a me lenalidomide e hoʻoulu i ka hoʻohaʻahaʻa ʻana o 6,572 kikoʻī C2H2 ZF kumu hoʻohālike i nā hiʻohiʻona kelepona. ʻO ka mea hope loa, ua ʻike ka poʻe noiʻi i ʻeono mau protein C2H2 ZF e lilo i mea maʻalahi i kēia mau lāʻau lapaʻau, ʻehā o ia mau mea ʻaʻole i manaʻo ʻia he mau pahuhopu no ka thalidomide a me kona ʻohana.

A laila hana nā mea noiʻi i ka hana a me ka hoʻolālā ʻana o IKZF1 a me IKZF3 e hoʻomaopopo maikaʻi i nā hana o ka pilina ma waena o nā mea transcription, cereblon a me kā lākou thalidomide. Ma waho aʻe o kēia, ua holo lākou i 4,661 mau hiʻohiʻona kamepiula mutational e ʻike inā hiki ke wānana ʻia nā kumu transcription ʻē aʻe e kuʻi me ka cereblon i mua o ka lāʻau. Ua hōʻike ka poʻe noiʻi i nā lāʻau lapaʻau e like me thalidomide i hoʻololi ʻia e pono e hoʻowalewale i ka cereblon e hōʻailona i nā isoforms kikoʻī o ka C2H2 ZF transcription factor e hoʻohana hou iā ia.