RAC1
RAC1Rac1은 Ras 관련 C3 보툴리눔 톡신 기질 1로도 알려져 있으며, 인간 세포에서 발견되는 단백질이다.그것은 RAC1 유전자에 의해 암호화된다.[5][6]이 유전자는 Rac1 단백질의 여러 가지 다른 분할 버전을 만들 수 있는데, 이것은 다른 기능을 수행하는 것으로 보인다.[7]
함수
Rac1은 G단백질(더 구체적으로는 GTPase)을 신호하는 작은 (~21kDa)이며, GTPases의 Rho 계열의 Rac 하위 계열의 일원이다.이 슈퍼 패밀리의 구성원들은 글루코스 섭취에 대한 글루트4[8][9] 변환 제어, 세포 성장, 세포 골격계 재구성, 항균 세포독성,[10] 단백질 키나제 활성화 등 다양한 셀룰러 이벤트를 규제하는 것으로 보인다.[11]
Rac1은 세포 주기, 세포-세포 접착, 운동성(액틴 네트워크를 통한) 및 상피 분화(피피질 줄기세포 유지에 필요한 것으로 제안됨)를 포함한 많은 세포 과정들의 플립방성 조절기다.
암에서의 역할
Rac과 Rho 단백질의 다른 하위 제품군과 함께, 그들은 세포 운동성과 세포 성장에 특히 중요한 규제 역할을 한다.Rac1은 유비쿼터스 조직표현을 가지고 있으며, 라멜리포디아의 형성에 의해 세포 운동성을 촉진한다.[12]암세포가 성장하여 국소 및 원거리 조직을 침범하기 위해서는 세포운동성 규제완화가 암세포의 침입과 전이에서 두드러진 사건 중 하나이다.[13]쥐에서 구성성 있는 활성 Rac1 V12의 과도한 압착은 표현적으로 카포시의 육종과 구별할 수 없는 종양을 유발했다.[14]Rac1의 기능상 돌연변이를 활성화하거나 활성화하는 것은 NEDD9과 DOK3 단백질 복합체가 지원하는 중피형 세포 운동을 촉진하는 데 적극적인 역할을 하는 것으로 보인다.[15]이러한 비정상적인 세포 운동성으로 인해 상피 중피 전이(EMT)가 발생할 수 있는데, 이는 종양 전이뿐만 아니라 약물 내성 종양 재발에 대한 추진 메커니즘이다.[16][17]
포도당 운반의 역할
Rac1은 지방 조직과 골격근과 같은 인슐린 민감 조직에서 상당한 양으로 표현된다.여기서 Rac1은 GLUT4 vesicle을 세포내 구획에서 플라즈마 막으로 운반하는 포도당의 변환을 규제했다.[9][18][19]인슐린에 반응하여, 이것은 혈당이 혈당을 낮추기 위해 세포 안으로 들어갈 수 있게 한다.비만과 제2형 당뇨병의 경우 골격근에 Rac1 신호가 기능장애가 있어 Rac1이 병의 진행에 기여함을 시사한다.Rac1 단백질은 운동과[8][20] 근육 스트레칭으로[21] 활성화된 골격근의 포도당 섭취에도 필요하다.
임상적 유의성
Rac1에서 돌연변이를 활성화시키는 것은 최근 흑색종과[22][23][24] 비소세포 폐암과 관련된 대규모 유전체 연구에서 발견되었다.[25]그 결과, Rac1은 이러한 많은 질병의 치료 대상으로 여겨지고 있다.[26]
최근의 몇몇 연구들은 또한 인간의 유방암뿐만 아니라 전이성 흑색종과 간암에서 Rac1 활동을 약리학적으로 억제함으로써 종양의 성장을 억제하는 표적 요법을 이용했다.[27][28][29]예를 들어 Rac1 의존 경로 억제 결과 종양세포 표현형식이 역전되어 Rac1이 트라스투주맙 내성 유방암의 예측표지자 치료목표로 제시되었다.[28]그러나 포도당 운반에 있어 Rac1의 역할을 감안할 때 Rac1을 억제하는 약물은 포도당 동점선상에 잠재적으로 해로울 수 있다.
지배적인 음수 또는 구성성 활성 세균라인 RAC1 돌연변이는 정신 지체 유형 48로 함께 그룹화된 다양한 표현형을 유발한다.[30]대부분의 돌연변이는 소두증을 유발하는 반면 어떤 특정한 변화는 대두증을 유발하는 것으로 보인다.
상호작용
RAC1은 다음과 상호 작용하는 것으로 나타났다.
참조
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- ^ Zhao C, Ma H, Bossy-Wetzel E, Lipton SA, Zhang Z, Feng GS (Sep 2003). "GC-GAP, a Rho family GTPase-activating protein that interacts with signaling adapters Gab1 and Gab2". The Journal of Biological Chemistry. 278 (36): 34641–53. doi:10.1074/jbc.M304594200. PMID 12819203.
- ^ Moon SY, Zang H, Zheng Y (Feb 2003). "Characterization of a brain-specific Rho GTPase-activating protein, p200RhoGAP". The Journal of Biological Chemistry. 278 (6): 4151–9. doi:10.1074/jbc.M207789200. PMID 12454018.
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- ^ Worthylake DK, Rossman KL, Sondek J (Dec 2000). "Crystal structure of Rac1 in complex with the guanine nucleotide exchange region of Tiam1". Nature. 408 (6813): 682–8. doi:10.1038/35047014. PMID 11130063. S2CID 4429919.
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추가 읽기
- Benitah SA, Frye M, Glogauer M, Watt FM (Aug 2005). "Stem cell depletion through epidermal deletion of Rac1". Science. 309 (5736): 933–5. doi:10.1126/science.1113579. PMID 16081735. S2CID 21888612.
- Ramakers GJ (Apr 2002). "Rho proteins, mental retardation and the cellular basis of cognition". Trends in Neurosciences. 25 (4): 191–9. doi:10.1016/S0166-2236(00)02118-4. PMID 11998687. S2CID 13941716.
- Esufali S, Charames GS, Bapat B (Oct 2007). "Suppression of nuclear Wnt signaling leads to stabilization of Rac1 isoforms". FEBS Letters. 581 (25): 4850–6. doi:10.1016/j.febslet.2007.09.013. PMID 17888911. S2CID 1457000.
외부 링크
- rac1+GTP-Binding+Protein(미국 국립 의학 라이브러리 의료 과목 제목)
- 셀 마이그레이션 게이트웨이에 링크가 있는 RAC1 정보