From Wikipedia, the free encyclopedia
Jump to: navigation, search
Myeloid cell leukemia sequence 1 (BCL2-related)
Protein MCL1 PDB 2nl9.png
PDB rendering based on 2nl9.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols MCL1 ; BCL2L3; EAT; MCL1-ES; MCL1L; MCL1S; Mcl-1; TM; bcl2-L-3; mcl1/EAT
External IDs OMIM159552 MGI101769 HomoloGene7413 ChEMBL: 4361 GeneCards: MCL1 Gene
RNA expression pattern
PBB GE MCL1 200797 s at tn.png
PBB GE MCL1 200796 s at tn.png
PBB GE MCL1 200798 x at tn.png
More reference expression data
Species Human Mouse
Entrez 4170 17210
Ensembl ENSG00000143384 ENSMUSG00000038612
UniProt Q07820 P97287
RefSeq (mRNA) NM_001197320 NM_008562
RefSeq (protein) NP_001184249 NP_032588
Location (UCSC) Chr 1:
150.55 – 150.55 Mb
Chr 3:
95.66 – 95.66 Mb
PubMed search [1] [2]

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


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[edit]

Omacetaxine mepesuccinate and Seliciclib [4] as an investigational treatment for chronic myelogenous leukemia (CML) and multiple myeloma respectively, act by inhibiting synthesis of Mcl-1.

See also[edit]


MCL1 has been shown to interact with BAK1,[5][6][7][8] Noxa,[6][9] BCL2L11,[8][9][10] Bcl-2-associated death promoter,[9][11] PCNA,[12] DAD1,[13] TNKS[14] and BH3 interacting domain death agonist.[7][9]


  1. ^ Kozopas KM, Yang T, Buchan HL, Zhou P, Craig RW (May 1993). "MCL1, a gene expressed in programmed myeloid cell differentiation, has sequence similarity to BCL2". Proc Natl Acad Sci U S A 90 (8): 3516–20. doi:10.1073/pnas.90.8.3516. PMC 46331. PMID 7682708. 
  2. ^ Craig RW, Jabs EW, Zhou P, Kozopas KM, Hawkins AL, Rochelle JM, Seldin MF, Griffin CA (February 1995). "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". Genomics 23 (2): 457–63. doi:10.1006/geno.1994.1523. PMID 7835896. 
  3. ^ "Entrez Gene: MCL1 myeloid cell leukemia sequence 1 (BCL2-related)". 
  4. ^ MacCallum DE, Melville J, Frame S, Watt K, Anderson S, Gianella-Borradori A, Lane DP, Green SR (2005). "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". Cancer Research 65 (12): 5399–5407. doi:10.1158/0008-5472.CAN-05-0233. PMID 15958589. 
  5. ^ Leu, J I-Ju; Dumont Patrick; Hafey Michael; Murphy Maureen E; George Donna L (May 2004). "Mitochondrial p53 activates Bak and causes disruption of a Bak-Mcl1 complex". Nat. Cell Biol. (England) 6 (5): 443–50. doi:10.1038/ncb1123. ISSN 1465-7392. PMID 15077116. 
  6. ^ a b Willis, Simon N; Chen Lin; Dewson Grant; Wei Andrew; Naik Edwina; Fletcher Jamie I; Adams Jerry M; Huang David C S (June 2005). "Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins". Genes Dev. (United States) 19 (11): 1294–305. doi:10.1101/gad.1304105. ISSN 0890-9369. PMC 1142553. PMID 15901672. 
  7. ^ a b Weng, Changjiang; Li Yuan; Xu Dan; Shi Yong; Tang Hong (March 2005). "Specific cleavage of Mcl-1 by caspase-3 in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in Jurkat leukemia T cells". J. Biol. Chem. (United States) 280 (11): 10491–500. doi:10.1074/jbc.M412819200. ISSN 0021-9258. PMID 15637055. 
  8. ^ a b Bae, J; Leo C P; Hsu S Y; Hsueh A J (August 2000). "MCL-1S, a splicing variant of the antiapoptotic BCL-2 family member MCL-1, encodes a proapoptotic protein possessing only the BH3 domain". J. Biol. Chem. (UNITED STATES) 275 (33): 25255–61. doi:10.1074/jbc.M909826199. ISSN 0021-9258. PMID 10837489. 
  9. ^ a b c d Chen, Lin; Willis Simon N; Wei Andrew; Smith Brian J; Fletcher Jamie I; Hinds Mark G; Colman Peter M; Day Catherine L; Adams Jerry M; Huang David C S (February 2005). "Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function". Mol. Cell (United States) 17 (3): 393–403. doi:10.1016/j.molcel.2004.12.030. ISSN 1097-2765. PMID 15694340. 
  10. ^ Hsu, S Y; Lin P; Hsueh A J (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. (UNITED STATES) 12 (9): 1432–40. doi:10.1210/me.12.9.1432. ISSN 0888-8809. PMID 9731710. 
  11. ^ Bae, J; Hsu S Y; Leo C P; Zell K; Hsueh A J (October 2001). "Underphosphorylated BAD interacts with diverse antiapoptotic Bcl-2 family proteins to regulate apoptosis". Apoptosis (United States) 6 (5): 319–30. doi:10.1023/A:1011319901057. ISSN 1360-8185. PMID 11483855. 
  12. ^ Fujise, K; Zhang D; Liu J; Yeh E T (December 2000). "Regulation of apoptosis and cell cycle progression by MCL1. Differential role of proliferating cell nuclear antigen". J. Biol. Chem. (UNITED STATES) 275 (50): 39458–65. doi:10.1074/jbc.M006626200. ISSN 0021-9258. PMID 10978339. 
  13. ^ Makishima, T; Yoshimi M; Komiyama S; Hara N; Nishimoto T (September 2000). "A subunit of the mammalian oligosaccharyltransferase, DAD1, interacts with Mcl-1, one of the bcl-2 protein family". J. Biochem. (JAPAN) 128 (3): 399–405. doi:10.1093/oxfordjournals.jbchem.a022767. ISSN 0021-924X. PMID 10965038. 
  14. ^ Bae, Jeehyeon; Donigian Jill R; Hsueh Aaron J W (February 2003). "Tankyrase 1 interacts with Mcl-1 proteins and inhibits their regulation of apoptosis". J. Biol. Chem. (United States) 278 (7): 5195–204. doi:10.1074/jbc.M201988200. ISSN 0021-9258. PMID 12475993. 

Further reading[edit]