세포핵항원증식

Proliferating cell nuclear antigen
PCNA
사용가능 구조물
PDBOrtholog 검색: PDBe RCSB
식별자
별칭PCNA, ATLD2 증식성 세포핵항원
외부 IDOMIM : 176740 MGI : 97503 호몰로 유전자 : 1945 유전자 카드 : PCNA
오솔로지스
종.인간을마우스
엔트레즈

5111

18538

앙상블

ENSG00000132646

ENSMUSG000027342

유니프로트

P12004

P17918

RefSeq(mRNA)

NM_182649
NM_002592

NM_011045

RefSeq (단백질)

NP_002583
NP_872590

NP_035175

위치(UCSC)Chr 20: 5.11 – 5.13 MbChr 2: 132.09 – 132.1 Mb
PubMed 검색[3][4]
위키데이터
사용자 보기/편집마우스 보기/편집
DNA가 결합된 PolD의 Cryo-EM 구조.PCNA 프로세스 콤플렉스

증식세포핵항원(PCNA)은 진핵세포에서 DNA 중합효소 γ의 가공성 인자로 작용하는 DNA 클램프로 복제에 필수적입니다.PCNA는 호모트리머(homotrier)로서 DNA를 둘러싸서 그 가공성을 달성하고, 여기서 DNA 복제, DNA 복구, 염색질 재형성 및 후성유전에 [5]관여하는 단백질을 모집하는 스캐폴드 역할을 합니다.

많은 단백질이 알려진 두 개의 PCNA 상호 작용 모티프 PCNA 상호 작용 모티프 (PIP) 박스와[6] AlkB homologue 2 PCNA 상호 작용 모티프 (APIM)[7]를 통해 PCNA와 상호 작용합니다. PIP-박스를 통해 PCNA에 결합하는 단백질은 주로 DNA 복제에 관여하는 반면 APIM을 통해 PCNA에 결합하는 단백질은 유전독성 [8]스트레스의 맥락에서 주로 중요합니다.

기능.

이 유전자에 의해 암호화된 단백질은 핵에서 발견되며 DNA 중합효소 델타의 보조 인자입니다.암호화된 단백질은 호모트리머의 역할을 하며 DNA 복제 동안 선도적인 가닥 합성의 공정성을 증가시키는 것을 돕습니다.DNA 손상에 대한 반응으로, 이 단백질은 편재되어 RAD6 의존적 DNA 복구 경로에 관여합니다.이 유전자에 대해 동일한 단백질을 암호화하는 두 개의 전사 변형이 발견되었습니다.이 유전자의 유사 유전자는 4번 염색체와 X번 [9]염색체에 기술되어 있습니다.

PCNA는 또한 [10]생명의 영역에서 단일 다기능 DNA 중합효소인 polD의 공정성 인자로서 고세균에서 발견됩니다.

DNA 합성 중 핵 내 발현

PCNA는 원래 세포 [11]주기의 DNA 합성 단계에서 세포의 핵에 발현되는 항원으로 확인되었습니다.단백질의 일부가 서열 분석되었고 그 서열은 cDNA [12]클론의 분리를 허용하는 데 사용되었습니다.PCNA는 DNA polymerase delta (Pol δ)를 DNA에 고정시키는 데 도움이 됩니다. PCNA는 ATPase의 AAA+ 클래스의 헤테로펜타미닉 멤버인 복제 인자 C (RFC)[14]의 작용을 통해 DNA에 고정됩니다[13].PCNA의 발현은 E2F 전사 인자-함유 [15]복합체의 제어 하에 있습니다.

DNA 복구 역할

DNA 중합효소 엡실론은 DNA 복구 동안 제거된 손상된 DNA 가닥의 재합성에 관여하기 때문에, PCNA는 DNA 합성과 DNA [17][18]복구 모두에 중요합니다.

PCNA는 또한 복제 후 복구(PRR)[19]로 알려진 DNA 손상 허용 경로에 관련되어 있습니다.PRR에는 두 가지 하위 경로가 있습니다. (1) 손상된 DNA 염기를 활성 부위에 통합할 수 있는 특수화된 DNA 중합효소에 의해 수행되는 형질전환 합성 경로는 (정지하는 일반적인 복제 중합효소와는 달리) 손상을 우회합니다.그리고 (2) 상동 재조합 기계의 모집에 의한 손상 우회를 포함하는 것으로 생각되는 제안된 "손상 스위치" 경로.PCNA는 이러한 경로의 활성화와 세포에 의해 이용되는 경로에 대한 선택에 중추적입니다.PCNA는 유비퀴틴에 [20]의해 번역 후 변형됩니다.PCNA 상의 라이신 번호 164의 모노-유비퀴틴은 형질전환 합성 경로를 활성화합니다.PCNA 상에서[20] 비-정통 라이신-63-결합된 폴리-유비키틴 사슬에 의한 이 모노-유비키틴의 확장은 템플릿 스위치 경로를 활성화하는 것으로 생각됩니다.또한, PCNA 라이신-164 (그리고 더 적은 정도로, 라이신-127)의 스모일화 (small ubiquitin-like modifier, SUMO에 의한)는 주형 스위치 [20]경로를 억제합니다.이러한 길항 효과는 스모일화된 PCNA가 상동 재조합의 [21]시작에 필수적인 Rad51 핵단백질 필라멘트를 파괴하는 역할을 하는 Srs2라고 불리는 DNA 헬리케이스를 모집하기 때문에 발생합니다.

PCNA결합단백질

PCNA는 많은 [22]단백질과 상호작용합니다.

상호작용

PCNA는 다음과 상호작용하는 것으로 나타났습니다.

APIM을 통해 PCNA와 상호작용하는 단백질은 인간 AlkB 상동성 2, TFIIS-L, TFII-I, Rad51B,[7] XPA,[88] ZRANB3 [89]및 FBH1을 [90]포함합니다.

사용하다

증식하는 세포핵항원(PCNA) 또는 Ki-67로 명명된 단일클론항체에 대한 항체는 다양한 신생물, 예를 들어 성상세포종의 등급화에 사용될 수 있습니다.진단과 예후 예측의 가치가 있을 수 있습니다.(항체 표지를 통해) PCNA의 핵 분포 이미지는 세포 [91]주기의 초기, 중기 및 말기 S 단계를 구별하는 데 사용될 수 있습니다.그러나 항체의 중요한 한계는 세포가 잠재적인 인공물로 이어지도록 고정되어야 한다는 것입니다.

한편, 살아있는 세포에서 복제와 수리의 역학 연구는 PCNA의 번역 융합을 도입함으로써 이루어질 수 있습니다.세포 투과성 복제 및/또는 수명이 짧은 세포는 형질전환의 필요성을 제거하고, 형질전환이 어려운 문제 및/또는 수명이 짧은 세포를 우회하기 위해 사용될 수 있습니다.이 펩티드는 살아있는 조직에서 사용될 수 있고 심지어 복제되는 세포와 [92]수리되는 세포를 구별할 수 있다는 독특한 장점을 제공합니다.

PCNA는 암 [93]치료에서 잠재적인 치료 표적입니다.2023년 국립 희망의 도시 의료원은 뚜렷한 [94]부작용을 일으키지 않으면서 종양 성장을 억제하는 것으로 보이는 AOH1996을 이용한 표적 화학 요법에 대한 전임상 연구를 발표했습니다.

참고 항목

참고문헌

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