MCL1

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MCL1
Protein MCL1 PDB 2nl9.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases MCL1, BCL2L3, EAT, MCL1-ES, MCL1L, MCL1S, Mcl-1, TM, bcl2-L-3, mcl1/EAT, myeloid cell leukemia 1, BCL2 family apoptosis regulator, BCL2 family apoptosis regulator
External IDs MGI: 101769 HomoloGene: 7413 GeneCards: MCL1
Gene location (Human)
Chromosome 1 (human)
Chr. Chromosome 1 (human)[1]
Chromosome 1 (human)
Genomic location for MCL1
Genomic location for MCL1
Band 1q21.2 Start 150,574,551 bp[1]
End 150,579,738 bp[1]
RNA expression pattern
PBB GE MCL1 200796 s at fs.png

PBB GE MCL1 200797 s at fs.png

PBB GE MCL1 200798 x at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_182763
NM_001197320
NM_021960

NM_008562

RefSeq (protein)

NP_001184249
NP_068779
NP_877495

NP_032588

Location (UCSC) Chr 1: 150.57 – 150.58 Mb Chr 3: 95.66 – 95.66 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Induced myeloid leukemia cell differentiation protein Mcl-1 is a protein that in humans is encoded by the MCL1 gene.[5][6]

Function[edit]

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.[7]

Clinical significance[edit]

Omacetaxine mepesuccinate (a drug approved for the treatment for chronic myelogenous leukemia (CML)) and Seliciclib [8] (which is under investigation as a potential multiple myeloma treatment) both act in part by inhibiting synthesis of Mcl-1.

Interactions[edit]

MCL1 has been shown to interact with:

See also[edit]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000143384 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000038612 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ 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 46331Freely accessible. PMID 7682708. 
  6. ^ 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. 
  7. ^ "Entrez Gene: MCL1 myeloid cell leukemia sequence 1 (BCL2-related)". 
  8. ^ 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. 
  9. ^ Leu JI, Dumont P, Hafey M, Murphy ME, George DL (May 2004). "Mitochondrial p53 activates Bak and causes disruption of a Bak-Mcl1 complex". Nat. Cell Biol. 6 (5): 443–50. doi:10.1038/ncb1123. PMID 15077116. 
  10. ^ a b Willis SN, Chen L, Dewson G, Wei A, Naik E, Fletcher JI, Adams JM, Huang DC (June 2005). "Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins". Genes Dev. 19 (11): 1294–305. doi:10.1101/gad.1304105. PMC 1142553Freely accessible. PMID 15901672. 
  11. ^ a b Weng C, Li Y, Xu D, Shi Y, Tang H (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. 280 (11): 10491–500. doi:10.1074/jbc.M412819200. PMID 15637055. 
  12. ^ a b Bae J, Leo CP, Hsu SY, Hsueh AJ (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. 275 (33): 25255–61. doi:10.1074/jbc.M909826199. PMID 10837489. 
  13. ^ a b c d 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. 
  14. ^ 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. 
  15. ^ 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. 
  16. ^ 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. 128 (3): 399–405. doi:10.1093/oxfordjournals.jbchem.a022767. PMID 10965038. 
  17. ^ Fujise K, Zhang D, Liu J, Yeh ET (December 2000). "Regulation of apoptosis and cell cycle progression by MCL1. Differential role of proliferating cell nuclear antigen". J. Biol. Chem. 275 (50): 39458–65. doi:10.1074/jbc.M006626200. PMID 10978339. 
  18. ^ Liu H, Peng HW, Cheng YS, Yuan HS, Yang-Yen HF (April 2005). "Stabilization and enhancement of the antiapoptotic activity of mcl-1 by TCTP". Mol Cell Biol. 25 (8): 3117–26. doi:10.1128/MCB.25.8.3117-3126.2005. PMC 1069602Freely accessible. PMID 15798198. 
  19. ^ Bae J, Donigian JR, Hsueh AJ (February 2003). "Tankyrase 1 interacts with Mcl-1 proteins and inhibits their regulation of apoptosis". J. Biol. Chem. 278 (7): 5195–204. doi:10.1074/jbc.M201988200. PMID 12475993. 

Further reading[edit]