STAT3

STAT3
STAT3
Stat3 structure.png
사용 가능한 구조
PDBOrtholog 검색: PDBe RCSB
식별자
에일리어스STAT3, ADMIO, APRF, HIES, 신호 변환기 및 전사 3, ADMIO1의 활성화제
외부 IDOMIM: 102582 MGI: 103038 HomoloGene: 7960 GeneCard: STAT3
맞춤법
종.인간마우스
엔트레즈

6774

20848

앙상블

ENSG00000168610

ENSMUSG00000004040

유니프로트

P40763

P42227

RefSeq(mRNA)

NM_011486
NM_213659
NM_213660

RefSeq(단백질)

NP_035616
NP_998824
NP_998825

장소(UCSC)Chr 17: 42.31 ~42.39 MbChr 11: 100.78 ~100.83 Mb
PubMed 검색[3][4]
위키데이터
인간 보기/편집마우스 표시/편집

신호변환기 및 전사활성화기(STAT3)는 인간에게 STAT3 [5]유전자에 의해 부호화되는 전사인자이다.STAT 단백질 패밀리의 일원입니다.

기능.

STAT3는 STAT 단백질 패밀리의 구성원입니다.사이토카인 및 성장인자에 반응하여 STAT3는 수용체 관련 야누스 키나아제(JAK)에 의해 인산화되어 호모 또는 헤테로디머를 형성하고 전사활성제로 작용하는 세포핵으로 전이된다.구체적으로는 인터페론, 표피성장인자(EGF), 인터류킨(IL-)5 및 IL-6 등의 리간드에 반응하여 티로신705의 인산화 후에 STAT3가 활성화된다.또한 STAT3의 활성화는 미토겐활성단백질키나아제([7][8]MAPK)[6]에 의한 세린727의 인산화 및 c-src 비수용체 티로신인산화효소를 통해 발생할 수 있다.STAT3는 세포 자극에 반응하여 다양한 유전자의 발현을 매개하며, 따라서 세포 성장과 아포토시스 [9]같은 많은 세포 과정에서 중요한 역할을 한다.

STAT3 결핍 쥐의 배아는 위경화가 [10]시작되는 배아 7일 이후로는 발달할 수 없다.이러한 발달 초기 단계에서 배아줄기세포(ESC)의 자가 재생을 위해 STAT3 활성화가 필요한 것으로 보인다.실제로, 다른 방법을 통해 STAT3가 활성화되면,[11] 생쥐 ESC 배양물에 공급되어 미분화 상태를 유지하는 LIF는 생략될 수 있다.

STAT3는 다양한 자가면역질환에 [12]관여하고 있는 TH17 도우미 T세포의 분화에 필수적이다.바이러스 감염 중 T세포에서 STAT3가 결핍된 생쥐는 Tfh 세포를 생성하는 능력에 장애를 보이고 항체 기반 [13]면역력을 유지하는 데 실패한다.

STAT3는 암 전이의 요인인 E-셀렉틴의 조절을 증가시켰다.[14]

STAT3의 과활성화는 COVID-19 감염과 다른 바이러스 [15][16]감염에서 발생한다.

임상적 의의

STAT3 유전자의 기능 상실은 뼈와 치아의 [17]발달 장애뿐만 아니라 재발 감염과 관련된 Hyperimun Globulin E 증후군을 초래한다.

STAT3 유전자의 기능상 돌연변이는 갑상선 질환, 당뇨병, 장염, 저혈액 [18]수치와 같은 다장기 조기 발병 자가면역질환을 일으키는 것으로 보고되었으며, 구성 STAT3 활성화는 다양한 인간 암과 관련이 있으며 일반적으로 [19][20][21][22]예후가 좋지 않음을 시사한다.그것은 증식 효과뿐만 아니라 [19]항아포토시스 효과도 있다.

STAT3는 다른 곳에서 언급된 바와 같이 다양한 경로를 통해 구성적으로 활성화됨으로써 종양 발생을 촉진할 수 있다.STAT3의 종양 억제제 역할도 [23][24][25]보고되었다.인간 교아종, 즉 뇌종양에 대한 보고서에서 STAT3는 종양의 돌연변이 배경에 따라 종양 발생 또는 종양 억제 역할을 하는 것으로 나타났다.PTEN-Akt-FOXO 축(억제제)과 백혈병 억제인자 수용체 베타(LIFRbeta)-STAT3 신호 경로(oncogenic) 사이의 직접적인 연관성이 나타났다.

암세포에서 STAT3의 활성 증가는 염증 유전자의 발현을 조절하는 단백질 복합체의 기능 변화를 초래하고, 그 결과 분비체 및 세포 표현형의 큰 변화, 종양에서의 활동 및 전이 [26]능력의 변화를 초래한다.

상호 작용

STAT3는 다음과 상호작용하는 것으로 나타났습니다.

Niclosamide는 STAT3 시그널링 [56]경로를 억제하는 것으로 보입니다.

니코틴아미드는 자연적으로 STAT3를 억제합니다.[57] 그러나 NAC(아세틸시스테인)는 STAT3 억제제를 [58]억제한다.

레퍼런스

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