6ms4

Structural highlights

Function

[MCTS1_HUMAN] Anti-oncogene that play a role in cell cycle regulation; decreases cell doubling time and anchorage-dependent growth; shortens the duration of G1 transit time and G1/S transition. When constituvely expressed, increases CDK4 and CDK6 kinases activity and CCND1/cyclin D1 protein level, as well as G1 cyclin/CDK complex formation. Plays a role as translation enhancer; Recruits the density-regulated protein/DENR and binds to the cap complex of the 5'-terminus of mRNAs, subsequently altering the mRNA translation profile; Up-regulates protein levels of BCL2L2, TFDP1, MRE11A, CCND1 and E2F1, while mRNA levels remains constant. Hyperactivates DNA damage signaling pathway; increased gamma-irradiation-induced phosphorylation of histone H2AX, and induces damage foci formation. Increases the overall number of chromosomal abnormalities such as larger chromosomes formation and multiples chromosomal fusions when overexpressed in gamma-irradiated cells. May play a role in promoting lymphoid tumor development: lymphoid cell lines overexpressing MCTS1 exhibit increased growth rates and display increased protection against apoptosis. May contribute to the pathogenesis and progression of breast cancer via promotion of angiogenesis through the decline of inhibitory THBS1/thrombospondin-1, and inhibition of apoptosis. Involved in the process of proteasome degradation to down-regulate Tumor suppressor p53/TP53 in breast cancer cell; Positively regulates phosphorylation of MAPK1 and MAPK3.^{[1] [2] [3] [4] [5] [6] [7] [8] [9]} [DENR_HUMAN] May be involved in the translation of target mRNAs by scanning and recognition of the initiation codon. Involved in translation initiation; promotes recruitmnet of aminoacetyled initiator tRNA to P site of 40S ribosomes. Can promote release of deacylated tRNA and mRNA from recycled 40S subunits following ABCE1-mediated dissociation of post-termination ribosomal complexes into subunits. Plays a role in the modulation of the translational profile of a subset of cancer-related mRNAs when recruited to the translational initiation complex by the oncogene MCTS1.^{[10] [11] [12]}

References

1. ↑ Prosniak M, Dierov J, Okami K, Tilton B, Jameson B, Sawaya BE, Gartenhaus RB. A novel candidate oncogene, MCT-1, is involved in cell cycle progression. Cancer Res. 1998 Oct 1;58(19):4233-7. PMID:9766643
2. ↑ Dierov J, Prosniak M, Gallia G, Gartenhaus RB. Increased G1 cyclin/cdk activity in cells overexpressing the candidate oncogene, MCT-1. J Cell Biochem. 1999 Sep 15;74(4):544-50. PMID:10440924
3. ↑ Herbert GB, Shi B, Gartenhaus RB. Expression and stabilization of the MCT-1 protein by DNA damaging agents. Oncogene. 2001 Oct 11;20(46):6777-83. PMID:11709712 doi:10.1038/sj.onc.1204881
4. ↑ Shi B, Hsu HL, Evens AM, Gordon LI, Gartenhaus RB. Expression of the candidate MCT-1 oncogene in B- and T-cell lymphoid malignancies. Blood. 2003 Jul 1;102(1):297-302. Epub 2003 Mar 13. PMID:12637315 doi:10.1182/blood-2002-11-3486
5. ↑ Levenson AS, Thurn KE, Simons LA, Veliceasa D, Jarrett J, Osipo C, Jordan VC, Volpert OV, Satcher RL Jr, Gartenhaus RB. MCT-1 oncogene contributes to increased in vivo tumorigenicity of MCF7 cells by promotion of angiogenesis and inhibition of apoptosis. Cancer Res. 2005 Dec 1;65(23):10651-6. PMID:16322206 doi:10.1158/0008-5472.CAN-05-0845
6. ↑ Hsu HL, Shi B, Gartenhaus RB. The MCT-1 oncogene product impairs cell cycle checkpoint control and transforms human mammary epithelial cells. Oncogene. 2005 Jul 21;24(31):4956-64. PMID:15897892 doi:10.1038/sj.onc.1208680
7. ↑ Reinert LS, Shi B, Nandi S, Mazan-Mamczarz K, Vitolo M, Bachman KE, He H, Gartenhaus RB. MCT-1 protein interacts with the cap complex and modulates messenger RNA translational profiles. Cancer Res. 2006 Sep 15;66(18):8994-9001. PMID:16982740 doi:66/18/8994
8. ↑ Hsu HL, Choy CO, Kasiappan R, Shih HJ, Sawyer JR, Shu CL, Chu KL, Chen YR, Hsu HF, Gartenhaus RB. MCT-1 oncogene downregulates p53 and destabilizes genome structure in the response to DNA double-strand damage. DNA Repair (Amst). 2007 Sep 1;6(9):1319-32. Epub 2007 Apr 6. PMID:17416211 doi:10.1016/j.dnarep.2007.02.028
9. ↑ Nandi S, Reinert LS, Hachem A, Mazan-Mamczarz K, Hagner P, He H, Gartenhaus RB. Phosphorylation of MCT-1 by p44/42 MAPK is required for its stabilization in response to DNA damage. Oncogene. 2007 Apr 5;26(16):2283-9. Epub 2006 Oct 2. PMID:17016429 doi:10.1038/sj.onc.1210030
10. ↑ Reinert LS, Shi B, Nandi S, Mazan-Mamczarz K, Vitolo M, Bachman KE, He H, Gartenhaus RB. MCT-1 protein interacts with the cap complex and modulates messenger RNA translational profiles. Cancer Res. 2006 Sep 15;66(18):8994-9001. PMID:16982740 doi:66/18/8994
11. ↑ Mazan-Mamczarz K, Gartenhaus RB. Post-transcriptional control of the MCT-1-associated protein DENR/DRP by RNA-binding protein AUF1. Cancer Genomics Proteomics. 2007 May-Jun;4(3):233-9. PMID:17878526
12. ↑ Skabkin MA, Skabkina OV, Dhote V, Komar AA, Hellen CU, Pestova TV. Activities of Ligatin and MCT-1/DENR in eukaryotic translation initiation and ribosomal recycling. Genes Dev. 2010 Aug 15;24(16):1787-801. doi: 10.1101/gad.1957510. PMID:20713520 doi:http://dx.doi.org/10.1101/gad.1957510