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MECOM
MDS1 and EVI1 complex locus protein (MECOM) also known as ecotropic virus integration site 1 protein homolog (EVI-1) or positive regulatory domain zinc finger protein 3 (PRDM3) is a protein that in humans is encoded by the MECOM gene. MECOM was first identified as a common retroviral integration site in AKXD murine myeloid tumors. It has since been identified in a plethora of other organisms, and seems to play a relatively conserved developmental role in embryogenesis. MECOM is a transcription factor involved in many signaling pathways for both coexpression and coactivation of cell cycle genes.
The MECOM gene is located in the human genome on chromosome 3 (3q26.2). The gene spans 60 kilobases and encodes 16 exons, 10 of which are protein-coding. The first in-frame ATG start codon is in exon 3.
A large number of transcript variations exist, encoding different isoforms or chimeric proteins. Some of the most common ones are:
The MECOM is primarily found in the nucleus, either soluble or bound to DNA. The 145kDa isoform is the most-studied, encoding 1051 amino acids, although there are many MECOM fusion products detectable in cells expressing MECOM.
The MECOM protein contains 2 domains characterized by 7 zinc finger motifs followed by a proline-rich transcription repression domain, 3 more zinc finger motifs and an acidic C-terminus.
MECOM is a proto-oncogene conserved across humans, mice, and rats, sharing 91% homology in nucleotide sequence and 94% homology in amino acid sequence between humans and mice. It is a transcription factor localized to the nucleus and binds DNA through specific conserved sequences of GACAAGATA with the potential to interact with both corepressors and coactivators.
MECOM has been described as a proto-oncogene since its first discovery in 1988. Overexpression and aberrant expression of MECOM has been associated with human acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS) and chronic myelogenous leukemia (CML), and more recently has been shown as a poor prognostic indicator. Its function in these cells may be regulated by phosphorylation of serine196, in its N-terminal DNA binding domain. All of these involve erratic cellular development and differentiation in the bone marrow leading to dramatic alterations in the normal population of blood cells. MECOM has also been found to play a role in solid ovarian and colon tumors, although it is not yet well characterized in this context. It has been hypothesized that it acts as a survival factor in tumor cell lines, preventing therapeutic-induced apoptosis and rendering the tumor cells more resistant to current treatments.
MECOM has been shown to be involved in the downstream signaling pathway of transforming growth factor beta (TGF-β). TGF-β, along with other TGF-β family ligands such as bone morphogenic protein (BMP) and activin are involved in regulating important cellular functions such as proliferation, differentiation, apoptosis, and matrix production. These biological roles are not only important for cellular development, but also in understanding oncogenesis.
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MECOM
MDS1 and EVI1 complex locus protein (MECOM) also known as ecotropic virus integration site 1 protein homolog (EVI-1) or positive regulatory domain zinc finger protein 3 (PRDM3) is a protein that in humans is encoded by the MECOM gene. MECOM was first identified as a common retroviral integration site in AKXD murine myeloid tumors. It has since been identified in a plethora of other organisms, and seems to play a relatively conserved developmental role in embryogenesis. MECOM is a transcription factor involved in many signaling pathways for both coexpression and coactivation of cell cycle genes.
The MECOM gene is located in the human genome on chromosome 3 (3q26.2). The gene spans 60 kilobases and encodes 16 exons, 10 of which are protein-coding. The first in-frame ATG start codon is in exon 3.
A large number of transcript variations exist, encoding different isoforms or chimeric proteins. Some of the most common ones are:
The MECOM is primarily found in the nucleus, either soluble or bound to DNA. The 145kDa isoform is the most-studied, encoding 1051 amino acids, although there are many MECOM fusion products detectable in cells expressing MECOM.
The MECOM protein contains 2 domains characterized by 7 zinc finger motifs followed by a proline-rich transcription repression domain, 3 more zinc finger motifs and an acidic C-terminus.
MECOM is a proto-oncogene conserved across humans, mice, and rats, sharing 91% homology in nucleotide sequence and 94% homology in amino acid sequence between humans and mice. It is a transcription factor localized to the nucleus and binds DNA through specific conserved sequences of GACAAGATA with the potential to interact with both corepressors and coactivators.
MECOM has been described as a proto-oncogene since its first discovery in 1988. Overexpression and aberrant expression of MECOM has been associated with human acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS) and chronic myelogenous leukemia (CML), and more recently has been shown as a poor prognostic indicator. Its function in these cells may be regulated by phosphorylation of serine196, in its N-terminal DNA binding domain. All of these involve erratic cellular development and differentiation in the bone marrow leading to dramatic alterations in the normal population of blood cells. MECOM has also been found to play a role in solid ovarian and colon tumors, although it is not yet well characterized in this context. It has been hypothesized that it acts as a survival factor in tumor cell lines, preventing therapeutic-induced apoptosis and rendering the tumor cells more resistant to current treatments.
MECOM has been shown to be involved in the downstream signaling pathway of transforming growth factor beta (TGF-β). TGF-β, along with other TGF-β family ligands such as bone morphogenic protein (BMP) and activin are involved in regulating important cellular functions such as proliferation, differentiation, apoptosis, and matrix production. These biological roles are not only important for cellular development, but also in understanding oncogenesis.