malignant T cell amplified sequence 1; MCT-1; multiple copies T-cell malignancies (MCTS1, MCT1)

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 a) recruits the density-regulated protein/DENR & binds to the cap complex of the 5'-terminus of mRNAs, subsequently altering the mRNA translation profile b) up-regulates protein levels of BCL2L2, TFDP1, MRE11A, CCND1 & E2F1, while mRNA levels remains constant - 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

Properties

SIZE: entity length = 181 aa MW = 21 kD COMPARTMENT: cytoplasm cell nucleus MOTIF: Thr phosphorylation site {T81} PUA {92-171} MOTIF: Ser phosphorylation site {S118}

Database Correlations

UniProt Q9ULC4 Pfam PF01472 Kegg hsa:2898

References

UniProt :accession Q9ULC4