malignant T cell amplified sequence 1; MCT-1; multiple copies T-cell malignancies (MCTS1, MCT1)
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Function
- anti-oncogene with role in cell cycle regulation
- decreases cell doubling time & anchorage-dependent growth
- shortens the duration of G1 transit time & G1/S transition.
- when constituvely expressed, increases CDK4 & CDK6 kinase activity & CCND1/cyclin D1 protein level, as well as G1 cyclin/CDK complex formation
- plays a role as translation enhancer
- hyperactivates DNA damage signaling pathway
- increases gamma-irradiation-induced phosphorylation of histone H2AX, & induces damage foci formation
- increases the overall number of chromosomal abnormalities such as larger chromosomes formation & multiples chromosomal fusions when over-expressed in gamma-irradiated cells
- may play a role in promoting lymphoid tumor development: lymphoid cell lines over-expressing MCTS1 exhibit increased growth rates & display increased protection against apoptosis
- positively regulates phosphorylation of MAPK1 & MAPK3
- interacts (via PUA domain) with DENR
- phosphorylation is critical for stabilization & promotion of cell proliferation
Structure
- the PUA RNA-binding domain is critical for cap binding, but not sufficient for translation enhancer function
- MCT1 N-terminal region is required to enhance translation possibly trough interaction with other proteins
- belongs to the MCTS1 family
- contains 1 PUA domain
Compartment
- cytoplasm
- nuclear relocalization after DNA damage
Alternative splicing
named isoforms=2
Expression
- ubiquitous
- induced by DNA damaging agents such as gamma irradiation, adriamycin or taxol in lymphoid cells, but not by stress stimuli such as heat shock; induction of protein expression does not occur at the RNA level, & does not require new protein synthesis
Pathology
- may contribute to pathogenesis & progression of breast cancer via promotion of angiogenesis through the decline of inhibitory THBS1/thrombospondin-1, & inhibition of apoptosis
- role in proteosome degradation to down-regulate tumor suppressor p53/TP53 in breast cancer cells
- over-expressed in T-cell lymphoid cell lines & in non-Hodgkin lymphoma cell lines as well as in a subset of primary large B-cell lymphomas