호모사피엔스 종의 단백질 코딩 유전자
BCL-2 유사 단백질 2 는 인간에서 14번 염색체 (밴드 q11.2-q12)의 BCL2L2 유전자 에 의해 인코딩되는 193-아미노산 단백질이다.[5] [6] [7] 원래는 레오니 깁슨, 수잔 코리 , 그리고 월터와 엘리자 홀 의학 연구소 의 동료들에 의해 발견되었는데, 그는 이것을 Bcl-w 라고 불렀다.[8]
함수 이 유전자는 bcl-2 단백질 계열 의 프로생존(항복제 ) 부재를 암호화하고 있으며, Bcl-xL 과 가장 유사하다.[7] 이 가족의 단백질은 이성애자 또는 호모디머를 형성하고 반독점적 규제자 역할을 한다. 세포에서 이 유전자의 발현이 세포독성 조건에서 세포사멸 감소에 기여하는 것으로 나타났다. 생쥐의 관련 유전자에 대한 연구는 NGF-와 BDNF 의존성 뉴런의 생존에 대한 역할을 나타냈다. 쥐 유전자의 돌연변이와 녹아웃 연구는 성인의 정조세포화 에 필수적인 역할을 했다.[6] [9] [7]
임상적 유의성 교모세포종 , 대장암 , 비소세포 폐암 , 유방암 등 많은 암에서 높은 수준의 Bcl-w가 나타난다.[7] 전이성 유방암 환자는 1차 종양 만 있는 유방암 환자보다 Bcl-w가 높다.[7] Bcl-w의 높아진 수치는 아밀로이드 베타 에 의해 유발된 세포 죽음으로부터 뉴런 을 보호하는 것으로 나타났다.[7] 돌연변이 PARK2 유전자를 가진 파킨슨병 환자 가 Bcl-w를 상승시켰다.[7] Bcl-w는 세포 노화 에 기여하는 것으로 나타났다.[7]
Quercetin 은 Bcl-w의 다운규제 로 이어지는 PI3K/AKT 경로 를 억제하는 것으로 나타났다.[10] [7]
상호작용 BCL2L2는 다음 과 상호 작용하는 것으로 나타났다.
참조 ^ a b c GRCh38: 앙상블 릴리스 89: ENSG00000129473 - 앙상블 , 2017년 5월^ a b c GRCm38: 앙상블 릴리스 89: ENSMUSG000089682 - 앙상블 , 2017년 5월^ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ Gibson L, Holmgreen SP, Huang DC, Bernard O, Copeland NG, Jenkins NA, Sutherland GR , Baker E, Adams JM, Cory S (October 1996). "bcl-w, a novel member of the bcl-2 family, promotes cell survival". Oncogene . 13 (4): 665–75. PMID 8761287 . ^ a b "Entrez Gene: BCL2L2 BCL2-like 2" .^ a b c d e f g h i Hartman ML, Czyz M (2020). "BCL-w: apoptotic and non-apoptotic role in health and disease" . Cell Death & Disease . 11 (4): 2260. doi :10.1038/s41419-020-2417-0 . PMC 7174325 PMID 32317622 . ^ Gibson L, Holmgreen SP, Huang DC, et al. (1996). "bcl-w, a novel member of the bcl-2 family, promotes cell survival". Oncogene . 13 (4): 665–75. PMID 8761287 . ^ Kelly, Gemma L.; Strasser, Andreas (2020). "Toward Targeting Antiapoptotic MCL-1 for Cancer Therapy" . Annual Review of Cancer Biology . 4 : 299–313. doi :10.1146/annurev-cancerbio-030419-033510 ^ Paez-Ribes M, González-Gualda E, Doherty GJ, Muñoz-Espín D (2019). "Targeting senescent cells in translational medicine" . EMBO Molecular Medicine 11 (12): e10234. doi :10.15252/emmm.201810234 . PMC 6895604 PMID 31746100 . ^ Hsu SY, Lin P, Hsueh AJ (September 1998). "BOD (Bcl-2-related ovarian death gene) is an ovarian BH3 domain-containing proapoptotic Bcl-2 protein capable of dimerization with diverse antiapoptotic Bcl-2 members" . Mol. Endocrinol . 12 (9): 1432–40. doi :10.1210/mend.12.9.0166 PMID 9731710 . ^ O'Connor L, Strasser A, O'Reilly LA, Hausmann G, Adams JM, Cory S, Huang DC (January 1998). "Bim: a novel member of the Bcl-2 family that promotes apoptosis" . EMBO J . 17 (2): 384–95. doi :10.1093/emboj/17.2.384 . PMC 1170389 PMID 9430630 . ^ a b Ayllón V, Cayla X, García A, Fleischer A, Rebollo A (July 2002). "The anti-apoptotic molecules Bcl-xL and Bcl-w target protein phosphatase 1alpha to Bad" . Eur. J. Immunol . 32 (7): 1847–55. doi :10.1002/1521-4141(200207)32:7<1847::AID-IMMU1847>3.0.CO;2-7 PMID 12115603 . ^ Chen L, Willis SN, Wei A, Smith BJ, Fletcher JI, Hinds MG, Colman PM, Day CL, Adams JM, Huang DC (February 2005). "Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function" . Mol. Cell . 17 (3): 393–403. doi :10.1016/j.molcel.2004.12.030 PMID 15694340 . ^ Bae J, Hsu SY, Leo CP, Zell K, Hsueh AJ (October 2001). "Underphosphorylated BAD interacts with diverse antiapoptotic Bcl-2 family proteins to regulate apoptosis". Apoptosis . 6 (5): 319–30. doi :10.1023/A:1011319901057 . PMID 11483855 . S2CID 23119757 . ^ Holmgreen SP, Huang DC, Adams JM, Cory S (June 1999). "Survival activity of Bcl-2 homologs Bcl-w and A1 only partially correlates with their ability to bind pro-apoptotic family members" . Cell Death Differ . 6 (6): 525–32. doi :10.1038/sj.cdd.4400519 PMID 10381646 .
추가 읽기 Nagase T, Seki N, Ishikawa K, et al. (1997). "Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain" . DNA Res . 3 (5): 321–9, 341–54. doi :10.1093/dnares/3.5.321 PMID 9039502 . O'Connor L, Strasser A, O'Reilly LA, et al. (1998). "Bim: a novel member of the Bcl-2 family that promotes apoptosis" . EMBO J . 17 (2): 384–95. doi :10.1093/emboj/17.2.384 . PMC 1170389 PMID 9430630 . Ross AJ, Waymire KG, Moss JE, et al. (1998). "Testicular degeneration in Bclw-deficient mice". Nat. Genet . 18 (3): 251–6. doi :10.1038/ng0398-251 . PMID 9500547 . S2CID 32843609 . Hsu SY, Lin P, Hsueh AJ (1998). "BOD (Bcl-2-related ovarian death gene) is an ovarian BH3 domain-containing proapoptotic Bcl-2 protein capable of dimerization with diverse antiapoptotic Bcl-2 members" . Mol. Endocrinol . 12 (9): 1432–40. doi :10.1210/mend.12.9.0166 PMID 9731710 . Middleton G, Wyatt S, Ninkina N, Davies AM (2001). "Reciprocal developmental changes in the roles of Bcl-w and Bcl-x(L) in regulating sensory neuron survival". Development . 128 (3): 447–57. doi :10.1242/dev.128.3.447 . PMID 11152643 . O'Reilly LA, Print C, Hausmann G, et al. (2001). "Tissue expression and subcellular localization of the pro-survival molecule Bcl-w" . Cell Death Differ . 8 (5): 486–94. doi :10.1038/sj.cdd.4400835 PMID 11423909 . Bae J, Hsu SY, Leo CP, et al. (2001). "Underphosphorylated BAD interacts with diverse antiapoptotic Bcl-2 family proteins to regulate apoptosis". Apoptosis . 6 (5): 319–30. doi :10.1023/A:1011319901057 . PMID 11483855 . S2CID 23119757 . Puthalakath H, Villunger A, O'Reilly LA, et al. (2001). "Bmf: a proapoptotic BH3-only protein regulated by interaction with the myosin V actin motor complex, activated by anoikis". Science . 293 (5536): 1829–32. Bibcode :2001Sci...293.1829P . doi :10.1126/science.1062257 . PMID 11546872 . S2CID 5638023 . Ayllón V, Cayla X, García A, et al. (2002). "The anti-apoptotic molecules Bcl-xL and Bcl-w target protein phosphatase 1alpha to Bad" . Eur. J. Immunol . 32 (7): 1847–55. doi :10.1002/1521-4141(200207)32:7<1847::AID-IMMU1847>3.0.CO;2-7 PMID 12115603 . Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences" . Proc. Natl. Acad. Sci. U.S.A . 99 (26): 16899–903. doi :10.1073/pnas.242603899 PMC 139241 PMID 12477932 . Denisov AY, Madiraju MS, Chen G, et al. (2003). "Solution structure of human BCL-w: modulation of ligand binding by the C-terminal helix" . J. Biol. Chem . 278 (23): 21124–8. doi :10.1074/jbc.M301798200 PMID 12651847 . Hinds MG, Lackmann M, Skea GL, et al. (2003). "The structure of Bcl-w reveals a role for the C-terminal residues in modulating biological activity" . EMBO J . 22 (7): 1497–507. doi :10.1093/emboj/cdg144 . PMC 152889 PMID 12660157 . Wilson-Annan J, O'Reilly LA, Crawford SA, et al. (2003). "Proapoptotic BH3-only proteins trigger membrane integration of prosurvival Bcl-w and neutralize its activity" . J. Cell Biol . 162 (5): 877–87. doi :10.1083/jcb.200302144 . PMC 2172834 PMID 12952938 . Zhu X, Wang Y, Ogawa O, et al. (2004). "Neuroprotective properties of Bcl-w in Alzheimer disease" . J. Neurochem . 89 (5): 1233–40. doi :10.1111/j.1471-4159.2004.02416.x PMID 15147516 . Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)" . Genome Res . 14 (10B): 2121–7. doi :10.1101/gr.2596504 . PMC 528928 PMID 15489334 . Chen L, Willis SN, Wei A, et al. (2005). "Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function" . Mol. Cell . 17 (3): 393–403. doi :10.1016/j.molcel.2004.12.030 PMID 15694340 . Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes" . Genome Res . 16 (1): 55–65. doi :10.1101/gr.4039406 . PMC 1356129 PMID 16344560 . Denisov AY, Chen G, Sprules T, et al. (2006). "Structural model of the BCL-w-BID peptide complex and its interactions with phospholipid micelles". Biochemistry . 45 (7): 2250–6. doi :10.1021/bi052332s . PMID 16475813 . Certo M, Del Gaizo Moore V, Nishino M, et al. (2006). "Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members" . Cancer Cell . 9 (5): 351–65. doi :10.1016/j.ccr.2006.03.027 PMID 16697956 . 외부 링크
PDB 갤러리
1mk3 : 인간 BCL-W 단백질의 용액 구조
1o0l : BCL-W 구조는 생물학적 활동을 변조하는 데 있어 C-단자 잔류물의 역할을 나타낸다.
1zy3 : 비드 BH3-펩타이드 Bcl-w 단백질의 복합체 구조모델