MCL1

Myeloid cell leukemia sequence 1 (BCL2-related)
PDB rendering based on 2nl9.
Available structures PDB 2KBW, 2NL9, 2NLA, 2PQK, 3D7V, 3IO9, 3KJ0, 3KJ1, 3KJ2, 3KZ0, 3MK8
Identifiers
Symbols	MCL1; BCL2L3; EAT; MCL1-ES; MCL1L; MCL1S; MGC104264; MGC1839; Mcl-1; TM; bcl2-L-3; mcl1/EAT
External IDs	OMIM: 159552 MGI: 101769 HomoloGene: 7413 GeneCards: MCL1 Gene
Gene Ontology Molecular function • protein binding • protein channel activity • protein heterodimerization activity • BH3 domain binding Cellular component • nucleus • nucleoplasm • cytoplasm • mitochondrion • mitochondrial outer membrane • mitochondrial matrix • membrane • integral to membrane Biological process • cell fate determination • apoptosis • anti-apoptosis • multicellular organismal development • cellular homeostasis • cell differentiation • response to cytokine stimulus Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4170	17210
Ensembl	ENSG00000143384	ENSMUSG00000038612
UniProt	Q07820	P97287
RefSeq (mRNA)	NM_001197320.1	NM_008562.3
RefSeq (protein)	NP_001184249.1	NP_032588.1
Location (UCSC)	Chr 1: 150.55 – 150.55 Mb	Chr 3: 95.46 – 95.47 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]

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, as an investigational treatment for chronic myelogenous leukemia (CML), acts by inhibiting synthesis of Mcl-1.

See also

• Bcl-2

Interactions

MCL1 has been shown to interact with BAK1,^[4][5][6][7] Noxa,^[8][5] BCL2L11,^[8][7][9] Bcl-2-associated death promoter,^[10][8] PCNA,^[11] DAD1,^[12] TNKS^[13] and BH3 interacting domain death agonist.^[8][6]

References

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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=46331. 
2. ^ Craig RW, Jabs EW, Zhou P, Kozopas KM, Hawkins AL, Rochelle JM, Seldin MF, Griffin CA (Feb 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)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4170. 
4. ^ 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. 
5. ^ ^{a b} Willis, Simon N; Chen Lin, Dewson Grant, Wei Andrew, Naik Edwina, Fletcher Jamie I, Adams Jerry M, Huang David C S (Jun. 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1142553. 
6. ^ ^{a b} Weng, Changjiang; Li Yuan, Xu Dan, Shi Yong, Tang Hong (Mar. 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. 
7. ^ ^{a b} Bae, J; Leo C P, Hsu S Y, Hsueh A J (Aug. 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. 
8. ^ ^{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 (Feb. 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. 
9. ^ Hsu, S Y; Lin P, Hsueh A J (Sep. 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. 
10. ^ Bae, J; Hsu S Y, Leo C P, Zell K, Hsueh A J (Oct. 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. 
11. ^ Fujise, K; Zhang D, Liu J, Yeh E T (Dec. 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. 
12. ^ Makishima, T; Yoshimi M, Komiyama S, Hara N, Nishimoto T (Sep. 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. ISSN 0021-924X. PMID 10965038. 
13. ^ Bae, Jeehyeon; Donigian Jill R, Hsueh Aaron J W (Feb. 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

• Yang-Yen HF (2006). "Mcl-1: a highly regulated cell death and survival controller.". J. Biomed. Sci. 13 (2): 201–4. doi:10.1007/s11373-005-9064-4. PMID 16456709.