MCL1 (Mus musculus)
Description [+]
- Synonyms: MCL1, MCL1, MYELOID CELL LEUKEMIA SEQUENCE 1
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Rodentia; Mus musculus
- Short gene description: Induced myeloid leukemia cell differentiation protein Mcl-1 homolog (Bcl-2-related protein EAT/mcl1) [Source:UniProtKB/Swiss-Prot;Acc:P97287]
- Family: Bcl-2 family : multidomain Bcl-2
- Process: apoptosis,
- Pathways: intrinsic pathway, pre-mitochondrial signaling events,
- Criteria: manually curated
- Curator comment:
- WIKI: MCL1-M_musculus
References [+]
- Mcl-1, a Bcl-2 family member, delays the death of hematopoietic cells under a variety of apoptosis-inducing conditions.
- Zhou P, Qian L, Kozopas KM, Craig RW
- Mcl-1 is a member of the Bcl-2 family that was identified based on increased expression in myeloblastic leukemia cells undergoing differentiation. Mcl-1 was previously found to be similar to Bcl-2 in causing a delay in apoptotic cell death in Chinese hamster ovary cells. The work described here was aimed at determining whether Mcl-1 could also exert such an effect in hematopoietic cells, because endogenous Mcl-1 expression is prominent in the hematopoietic system. A further aim was to assess the effects of Mcl-1 in cells exposed to a variety of cytotoxic stimuli, because Bcl-2 is known to have a broad spectrum of activity. To approach these aims, FDC-P1 murine myeloid progenitor cells were transfected with vectors driving either constitutive or inducible expression of Mcl-1. The introduced Mcl-1 gene was found to cause a prolongation of viability under various conditions that cause apoptotic cell death, including exposure to cytotoxic agents (the chemotherapeutic drug etoposide, calcium ionophore, or UV irradiation) and the withdrawal of required growth factors. In addition, Mcl-1 was found to interact with Bax, a member of the Bcl-2 family that promotes cell death as a homodimer but that can heterodimerize with Bcl-2 to promote cell viability. Although Mcl-1 prolonged cell viability, it did not prevent eventual cell death upon continuous exposure to a cytotoxic agent. Prolongation of viability was maximal when expression of Mcl-1 was induced before the application of the apoptotic stimulus, although some increase occurred if Mcl-1 was induced shortly thereafter and before overt apoptosis. Taken as a whole, these findings provide further parallels between Mcl-1 and Bcl-2, showing that Mcl-1 can interact with Bax in hematopoietic FDC-P1 cells and can prolong cell viability under a variety of cytotoxic conditions. Blood. 1997 Jan 15;89(2):630-43.
- Knockout of myeloid cell leukemia-1 induces liver damage and increases apoptosis susceptibility of murine hepatocytes.
- Vick B, Weber A, Urbanik T, Maass T, Teufel A, Krammer PH, Opferman JT, Schuchmann M, Galle PR, Schulze-Bergkamen H
- Myeloid cell leukemia-1 (Mcl-1) is an antiapoptotic member of the Bcl-2 protein family. It interacts with proapoptotic Bcl-2 family members, thereby inhibiting mitochondrial activation and induction of apoptosis. Mcl-1 is essential for embryonal development and the maintenance of B cells, T cells, and hematopoietic stem cells. We have recently shown that induction of Mcl-1 by growth factors rescues primary human hepatocytes from CD95-mediated apoptosis. This prompted us to further analyze the relevance of Mcl-1 for hepatocellular homeostasis. Therefore, we generated a hepatocyte-specific Mcl-1 knockout mouse (Mcl-1(flox/flox)-AlbCre). Deletion of Mcl-1 in hepatocytes results in liver cell damage caused by spontaneous induction of apoptosis. Livers of Mcl-1(flox/flox)-AlbCre mice are smaller compared to control littermates, due to higher apoptosis rates. As a compensatory mechanism, proliferation of hepatocytes is enhanced in the absence of Mcl-1. Importantly, hepatic pericellular fibrosis occurs in Mcl-1 negative livers in response to chronic liver damage. Furthermore, Mcl-1(flox/flox)-AlbCre mice are more susceptible to hepatocellular damage induced by agonistic anti-CD95 antibodies or concanavalin A. Conclusion: The present study provides in vivo evidence that Mcl-1 is a crucial antiapoptotic factor for the liver, contributing to hepatocellular homeostasis and protecting hepatocytes from apoptosis induction. Hepatology. 2009 Feb;49(2):627-36.
Structure & Sequence [+]
Pfam domains:
(Pfam is a large collection of protein families.)
Source | Domain Name | Start | End |
---|---|---|---|
PFAM A | Bcl-2 | 194 | 293 |
Protein sequence [+]
Mcl1 | Mus musculus | 10090 | length:331
MFGLRRNAVIGLNLYCGGASLGAGGGSPAGARLVAEEAKARREGGGEAALLPGARVVARP
PPVGAEDPDVTASAERRLHKSPGLLAVPPEEMAASAAAAIVSPEEELDGCEPEAIGKRPA
VLPLLERVSEAAKSSGADGSLPSTPPPPEEEEDDLYRQSLEIISRYLREQATGSKDSKPL
GEAGAAGRRALETLRRVGDGVQRNHETAFQGMLRKLDIKNEGDVKSFSRVMVHVFKDGVT
NWGRIVTLISFGAFVAKHLKSVNQESFIEPLAETITDVLVRTKRDWLVKQRGWDGFVEFF
HVQDLEGGIRNVLLAFAGVAGVGAGLAYLIR
PPVGAEDPDVTASAERRLHKSPGLLAVPPEEMAASAAAAIVSPEEELDGCEPEAIGKRPA
VLPLLERVSEAAKSSGADGSLPSTPPPPEEEEDDLYRQSLEIISRYLREQATGSKDSKPL
GEAGAAGRRALETLRRVGDGVQRNHETAFQGMLRKLDIKNEGDVKSFSRVMVHVFKDGVT
NWGRIVTLISFGAFVAKHLKSVNQESFIEPLAETITDVLVRTKRDWLVKQRGWDGFVEFF
HVQDLEGGIRNVLLAFAGVAGVGAGLAYLIR
Structure links:
- Smartdomain prediction information: SM00337
- Prosite motif and domain information: PS01080
- Prosite motif and domain information: PS01258
- Prosite motif and domain information: PS01259
- Interpro domain information: P97287
- PFAM domain and domain family information: P97287
- Protein 3D structures from PDB: 1WSX 2ROC 2JM6 2ROD
Evolution [+]
View protein alignment and tree with Jalview:  
Explore tree at phylomeDB:   Click here.
Homologs list [+]
Name | Relationship | Species |
---|
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Gene Ontology [+]
GO id | Name | Ontology type | Evidence |
---|---|---|---|
GO:0007275 | multicellular organismal development | biological_proccess | IEA |
GO:0030154 | cell differentiation | biological_proccess | IEA |
GO:0042981 | regulation of apoptosis | biological_proccess | IEA |
GO:0006915 | apoptosis | biological_proccess | IEA |
GO:0034097 | response to cytokine stimulus | biological_proccess | ISO |
GO:0034097 | response to cytokine stimulus | biological_proccess | IEA |
GO:0005515 | protein binding | mollecular_function | IPI |
GO:0005515 | protein binding | mollecular_function | IEA |
GO:0046982 | protein heterodimerization activity | mollecular_function | IEA |
GO:0005634 | nucleus | cell_component | IEA |
GO:0005654 | nucleoplasm | cell_component | IEA |
GO:0005737 | cytoplasm | cell_component | IEA |
GO:0005739 | mitochondrion | cell_component | IEA |
GO:0016020 | membrane | cell_component | IEA |
GO:0016021 | integral to membrane | cell_component | IEA |
Check GO Evidence Codes here
Information from other databases [+]
- Gene info from MGI [?] MGI:101769
- Ensembl genome browser [?] : ENSMUSG00000038612
- Expression info from Arrayexpress [?] : ENSMUSG00000038612
- Protein expression from Protein Atlas: [?] ENSMUSG00000038612
- Community gene edition from Wikigenes: [?] 17210
Click on [?] for more information.