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词条 MCL1
释义

  1. Function

  2. Clinical significance

  3. Interactions

  4. See also

  5. References

  6. Further reading

{{Infobox_gene}}Induced myeloid leukemia cell differentiation protein Mcl-1 is a protein that in humans is encoded by the MCL1 gene.[1][2]

Function

The protein encoded by this gene belongs to the Bcl-2 family. Alternative splicing occurs at this locus and two transcript variants encoding distinct isoforms have been identified. The longer gene product (isoform 1) enhances cell survival by inhibiting apoptosis while the alternatively spliced shorter gene product (isoform 2) promotes apoptosis and is death-inducing.[3]

Clinical significance

Omacetaxine mepesuccinate (a drug approved for the treatment for chronic myelogenous leukemia (CML)) and Seliciclib [4] (which is under investigation as a potential multiple myeloma treatment) both act in part by inhibiting synthesis of Mcl-1.

Interactions

MCL1 has been shown to interact with:

  • BAK1,[5][6][7][8]
  • BCL2L11,[8][10][9]
  • BID,[7][10]
  • BAD,[10][10]
  • DAD1,[11]
  • PMAIP1,[6][12]
  • PCNA,[13]
  • TCTP[14] and
  • TNKS[15]

See also

  • Bcl-2
  • Bcl-xL

References

1. ^{{cite journal | vauthors = Kozopas KM, Yang T, Buchan HL, Zhou P, Craig RW | title = MCL1, a gene expressed in programmed myeloid cell differentiation, has sequence similarity to BCL2 | journal = Proc Natl Acad Sci U S A | volume = 90 | issue = 8 | pages = 3516–20 | date = May 1993 | pmid = 7682708 | pmc = 46331 | doi = 10.1073/pnas.90.8.3516 }}
2. ^{{cite journal | vauthors = Craig RW, Jabs EW, Zhou P, Kozopas KM, Hawkins AL, Rochelle JM, Seldin MF, Griffin CA | title = Human and mouse chromosomal mapping of the myeloid cell leukemia-1 gene: MCL1 maps to human chromosome 1q21, a region that is frequently altered in preneoplastic and neoplastic disease | journal = Genomics | volume = 23 | issue = 2 | pages = 457–63 | date = February 1995 | pmid = 7835896 | pmc = | doi = 10.1006/geno.1994.1523 }}
3. ^{{cite web | title = Entrez Gene: MCL1 myeloid cell leukemia sequence 1 (BCL2-related)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4170| accessdate = }}
4. ^{{cite journal | vauthors = MacCallum DE, Melville J, Frame S, Watt K, Anderson S, Gianella-Borradori A, Lane DP, Green SR | title = Seliciclib (CYC202, R-Roscovitine) induces cell death in multiple myeloma cells by inhibition of RNA polymerase II-dependent transcription and down-regulation of Mcl-1 | journal = Cancer Research | volume = 65 | issue = 12 | pages = 5399–5407 | year = 2005 | pmid = 15958589 | doi = 10.1158/0008-5472.CAN-05-0233 }}
5. ^{{cite journal | vauthors = Leu JI, Dumont P, Hafey M, Murphy ME, George DL | title = Mitochondrial p53 activates Bak and causes disruption of a Bak-Mcl1 complex | journal = Nat. Cell Biol. | volume = 6 | issue = 5 | pages = 443–50 | date = May 2004 | pmid = 15077116 | doi = 10.1038/ncb1123 }}
6. ^1 {{cite journal | vauthors = Willis SN, Chen L, Dewson G, Wei A, Naik E, Fletcher JI, Adams JM, Huang DC | title = Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins | journal = Genes Dev. | volume = 19 | issue = 11 | pages = 1294–305 | date = June 2005 | pmid = 15901672 | pmc = 1142553 | doi = 10.1101/gad.1304105 }}
7. ^1 {{cite journal | vauthors = Weng C, Li Y, Xu D, Shi Y, Tang H | title = Specific cleavage of Mcl-1 by caspase-3 in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in Jurkat leukemia T cells | journal = J. Biol. Chem. | volume = 280 | issue = 11 | pages = 10491–500 | date = March 2005 | pmid = 15637055 | doi = 10.1074/jbc.M412819200 }}
8. ^1 {{cite journal | vauthors = Bae J, Leo CP, Hsu SY, Hsueh AJ | title = MCL-1S, a splicing variant of the antiapoptotic BCL-2 family member MCL-1, encodes a proapoptotic protein possessing only the BH3 domain | journal = J. Biol. Chem. | volume = 275 | issue = 33 | pages = 25255–61 | date = August 2000 | pmid = 10837489 | doi = 10.1074/jbc.M909826199 }}
9. ^{{cite journal | vauthors = Hsu SY, Lin P, Hsueh AJ | title = 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 | journal = Mol. Endocrinol. | volume = 12 | issue = 9 | pages = 1432–40 | date = September 1998 | pmid = 9731710 | doi = 10.1210/mend.12.9.0166 }}
10. ^{{cite journal | vauthors = Bae J, Hsu SY, Leo CP, Zell K, Hsueh AJ | title = Underphosphorylated BAD interacts with diverse antiapoptotic Bcl-2 family proteins to regulate apoptosis | journal = Apoptosis | volume = 6 | issue = 5 | pages = 319–30 | date = October 2001 | pmid = 11483855 | doi = 10.1023/A:1011319901057 }}
11. ^{{cite journal | vauthors = Makishima T, Yoshimi M, Komiyama S, Hara N, Nishimoto T | title = A subunit of the mammalian oligosaccharyltransferase, DAD1, interacts with Mcl-1, one of the bcl-2 protein family | journal = J. Biochem. | volume = 128 | issue = 3 | pages = 399–405 | date = September 2000 | pmid = 10965038 | doi = 10.1093/oxfordjournals.jbchem.a022767 }}
12. ^1 2 3 {{cite journal | vauthors = Chen L, Willis SN, Wei A, Smith BJ, Fletcher JI, Hinds MG, Colman PM, Day CL, Adams JM, Huang DC | title = Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function | journal = Mol. Cell | volume = 17 | issue = 3 | pages = 393–403 | date = February 2005 | pmid = 15694340 | doi = 10.1016/j.molcel.2004.12.030 }}
13. ^{{cite journal | vauthors = Fujise K, Zhang D, Liu J, Yeh ET | title = Regulation of apoptosis and cell cycle progression by MCL1. Differential role of proliferating cell nuclear antigen | journal = J. Biol. Chem. | volume = 275 | issue = 50 | pages = 39458–65 | date = December 2000 | pmid = 10978339 | doi = 10.1074/jbc.M006626200 }}
14. ^{{cite journal | vauthors = Liu H, Peng HW, Cheng YS, Yuan HS, Yang-Yen HF| title = Stabilization and enhancement of the antiapoptotic activity of mcl-1 by TCTP | journal = Mol Cell Biol | volume = 25 | issue = 8 | pages = 3117–26 | date = April 2005 | pmid = 15798198 | doi = 10.1128/MCB.25.8.3117-3126.2005 | pmc=1069602}}
15. ^{{cite journal | vauthors = Bae J, Donigian JR, Hsueh AJ | title = Tankyrase 1 interacts with Mcl-1 proteins and inhibits their regulation of apoptosis | journal = J. Biol. Chem. | volume = 278 | issue = 7 | pages = 5195–204 | date = February 2003 | pmid = 12475993 | doi = 10.1074/jbc.M201988200 }}

Further reading

{{refbegin}}
  • {{cite journal | vauthors = Yang-Yen HF | title = Mcl-1: a highly regulated cell death and survival controller. | journal = J. Biomed. Sci. | volume = 13 | issue = 2 | pages = 201–4 | year = 2006 | pmid = 16456709 | doi = 10.1007/s11373-005-9064-4 }}
{{refend}}{{PDB Gallery|geneid=4170}}{{gene-1-stub}}
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