
madhyam 1

trimp 18 ennum ariyappedunna trimptaitt motif kudumbatthil (trim) pedunna oru proteinaan midu 1. "midu 1" jeane ex chromosominte hraswa bhujathilaanu sthithicheyyunnathu, eee jeenile loss-oof-function mutationukal apoorva vikasana rogamaaya opitts jii/bbb syndrominte ex-linked roopathinu kaaranamaakunnu.
midu 1" jean athinte uthppannavum.
manushyante "midu 1" jeane x chromosominte (xp22.2) cheria kaiyilaanu sthithicheyyunnathu, athil ekadesham 400 keey. bii. genome vyaapichukidakkunna 9 coding exonukal ulppedunnu. aadyathe coding exonylake mukalilekku, "midu 1" jeane badal 5 'vivarthanam cheyyaatha exonukalum kuranjathu anchu badal promotermaarum jeeninte transcription nayikkunnu, athinte falamaayi niravadhi "midu 1" traanskript isophomukal undaakunnu. midu 1" jeane trim kudumbatthilppetta 667 amino assid proteine encode cheiyunnu. midu 1 proteinil oru ring domaine, 2 bii-boxes domainukal (bii-boxes 1, bii-boxes 2), oru coiled-koyil mekhala enniva ulkkollunna oru samrakshitha enn-terminal tripartite module adangiyirikkunnu. trim kudumbatthinullil, midu 1 ennathu sii-aii upavibhaagathil pedunnu, oru koos domaininte thri-kakshi rooparekhayude thaazhekku, oru fibronectin tharam III (efn 3) aavarthanam, oru prai-spry domaine ennivayude saannidhyam.
midu 1 pradhana sellular pravartthanangal.
midu 1 oru iii 3 ubiquitin ligase aayi.
koshangalilum inn vitroyilum ubiquitin iii3 ligezai pravartthikkunna oru microtubular proteinaan midu 1. onno athiladhikamo ubiquitin pepttaid thanmathrakal substrateukalilekku kaimaattam cheiyunnathu avayude sthirathayum/allengil pravartthanavum nirnnayikkunna oru tharam poost-translation parishkkaranamaan ubiquitination. madhya 1 e3 ubiquitin ligase pravartthanam ring domaine uthejippikkunnu, ithu iii 3 ubiquitin ligasukalude pradhana klaasukalilonninte mukhamudrayaanu, ithu ubiquitin cascadinullil ubiquitin pepttaid nirddishta substrateukalilekku kaimaran sahayikkunnu. alfa 4 (α4) umm athumaayi bandhapetta phosphatase, pipi 2 eiii, phu, paiks 6, braf 35 enningane niravadhi midu 1 iii 3 ubiquitin ligase targettukal report cheyyappettittund.
madhyam 1-α4-pp2a complexes.
α4, pp2a ennivaykkoppam, midu 1 nuu oru tritala samuchayam roopeekarikkaan kazhiyum, athil α4 oru adapter proteinaayi pravartthikkunnu. midu 1 mono-ubicvitatione prothsaahippikkunnave ithuvare daatta soochippikkunnu, ithu calpine-ashrita pilarppilekku nayikkunnu, ithu pipi 2 eiii kaattalitik subunit (pipi 2 essy) polyubikvitteshanum protesomalile apachayathinum kaaranamaakunnu. pipi2eiii niravadhi sellular prakriyakalil ulppedunnathinaal, midu-1-α4-pipi2eiii ternery complexes avayil palathinteyum niyanthranatthil earppettirikkaam, pradhaanamaayum microtubilukalil. complexinu emtorch 1 signalling modulate cheyyaan kazhiyum; theerchayaayum pipi 2 eiii defosphorylationiloode emtorch 1 pravartthanatthe kuraykkunnu. pipi2eiiisiyude alavu kuraykkunnathiloode, midu 1 emtorch 1 signalling vardhippikkunnathinu kaaranamaakunnu. neremarichu, midu 1-nte abhaavamo pravartthana nashtamo aaya mutationukal pipi 2 eyude alavu vardhippikkunnathilke nayikkunnu, athinte anantharafalamaayi, empy 2 eiii taargettukalude pothuvaaya hypo-phosphorylationilekku, emtorch 1 ulppedunnu. emtorch 1-nte signalling cytoskelital dynamics, intra sellular transport, sell migration, autofagi, protein synthesis, sell metabolism ennivayil ulppedunnu, athinaal pii. pii 2 eiii. sii niyanthrikkunnathiloode midu 1, eee sellular prakriyakalil chilathil aathyanthikamayi ulppettirikkaam.
midu 1, soonik hedge hogg.
midu 1 soonik hedge hogg (shhaa) pathayum ulppedunnu. hedge hogg signalling pathayil ulppedunna kinace aaya fuvinte sarvvyaapithvavum protesomaline aasrayikkunna pilarppum midu 1 uthejippikkunnu. fuyude kinace domaininte villal nucleusile transcription factor jii. aii. 3 eiii (aaktivettar phoom) yude traanslokkeshane anukoolikkunnu. eee reethiyil, jii. aii. 3eiii. shhaa taargett jeenukalude aavishkaaram sajeevamaakkukayum ithu shhaa signalling vardhippikkunnathilke nayikkukayum cheiyunnu. midu 1 num shhaa paathaykkum edayilulla cross tokkine maathrukaa jeevikalile pareekshanathmaka thelivukalum pinthunaykkunnu.
bhroona vikasanathinidayile pankum aavishkaaravum.
"midu 1" ellah bhroona koshangalilum sarvavyaapiyaayi prakadippikkappedunnu, vikasana samayat oru pradhana pravartthanamundu. garbhaavasthayude vividha samayangalil "midu 1" traanscriptinte expression paatten padikkaan niravadhi maathrukaa jeevikal upayogichittundu eliyum kozhiyum senopus manushya bhroonangalum. bhroona vikasanathinte aadyaghattathil, "midu 1" ennathu aadima nodil prakadippikkunnu, avide nodile tanmatra asamathvam sthaapikkunnathil midu 1 pradhana punk vahikkunnu, ithu bhroona vikasanam purogamikkumbol lattaraalittiyude aadyakaala nirvachanathinu nirnaayakamaan. pinneedu bhroonajananathil, neurulation ghattathil, "midu 1" traanskript pradhaanamaayum neural foldukalude thalayotti mekhalayil nireekshikkappedunnu. midjesteshan muthal, "midu 1" traanscriptinte ettavum uyarnna alavu kendra naadeevyavasthayude valarunna compartmentukalilum vikasichukondirikkunna branchiyal kamanangal, craniophasial prakriyakal, opttik vesicle, hridayathilum dahananaalathilum eurogenital systethilum nireekshikkappedunnu.
klinikkal praadhaanyam.
opitts jii/bbb syndrome (exlos) (omim #300000) enna ex-linked roopamaaya apoorva janithaka rogamulla rogikalil ithu kaaranamaayi parivartthanam cheyyappettuvennu kandethiyathode "midu 1" jeane thiricharinju. madhyarekhayude gadanakalude bhroona vikasanathile vaikalyangalaal savisheshamaaya oru janmana undaakunna vaikalyamaan ex. loss. klinikkal adayaalangalude uyarnna vyathiyaanamaan ex. losinte savisheshatha, ex-linked aayathinal, purushanmaare saadhaaranayaayi badhikkunnu. ettavum kooduthal nireekshikkappedunna adayaalangal ivayaanu pradhaanamaayum clift lip, annaakk, frondall bosing, valia nassel bridge, loow-settu chevikal ennivayumaayi bandhapetta hypertellorism prathinidheekarikkunna dysmorphic savisheshathakal. exlos rogikalil larringo-trackio-esophageal asaadhaaranathakalum vividha digri-hypospadiakal pradhaanamaayum prathinidheekarikkunna baahya jananendria asaadhaaranathakalum pathivayi nireekshikkappedunnu. koodaathe, ex. ell. oo. ezz rogikalkku hridaya vaikalyangalum guda vaikalyangalum undaayekkaam. cerebellar vermis hypoplasia, boudhika vaikalyangalum vikasana kaalathaamasangalumkoppam corpus kalosathinte ajenisis allengil hypoplasia enniva prathinidheekarikkunna oru neurological gadakavum ex. loss kaanikkunnu. ex losinte kaaranamaaya jeane aayi ithu kandethiyathinushesham, ekadesham nooru vyathyastha rogakarikalaaya mutationukal "midu 1" jeenil vivarichittundu. opitts syndrominte rogakaarikalil mutationukalude tharavum vitharanavum pravartthana nashtappedal samvidaanam nirddeshikkunnundeng, rogathinte rogakaaranashaasthram ippozhum avyakthamaanu.
vaividhyamaarnna sellular samvidaanangalil athinte swaadheenam kanakkiledukkumbol, adhika klinikkal avasthakal "midu 1"-nte mattangalumaayi bandhappettirikkunnave vivarikkappedunnu. vaasthavathil, aasthma, cancer, neuro degeneration ennivayil "midu 1" yude edapedal report cheyyappettittund.

