THO complex subunit 5 homolog is a protein that in humans is encoded by the THOC5gene.THOC5 is a member of THO complex which is a subcomplex of the transcription/export complex (TREX). THOC5 is evolutionarily conserved in higher eukaryotes, however the exact roles of THOC5 in transcription and mRNA export are still unclear. THOC5 is phosphorylated by several protein kinases at multiple residues upon extracellular stimuli. These include stimulation with growth factors/cytokines/chemokines, or DNA damage reagents. Furthermore, THOC5 is a substrate for several oncogenic tyrosine kinases, suggesting that THOC5 may be involved in cancer development. Recent THOC5 knockout mouse data reveal that THOC5 is an essential element in the maintenance of stem cells and growth factor/cytokine-mediated differentiation/proliferation. Furthermore, depletion of THOC5 influences less than 1% of total mRNA export in the steady state, however it influences more than 90% of growth factor/cytokine induced genes. THOC5, thereby contributes to the 3′ processing and/or export of immediate-early genes induced by extracellular stimuli. These studies bring new insight into the link between the mRNA export complex and immediate-early gene response. The data from these studies also suggest that THOC5 may be a useful tool for studying stem cell biology, for modifying the differentiation processes and for cancer therapy.[1][2][3][4][5][6][7][8][9][10][11][12]
↑Tran DDH, Koch A and Tamura T. THOC5, a member of the mRNA export complex: a novel link between mRNA export machinery and signal transduction pathways in cell proliferation and differentiation. Cell Communication and Signaling 2014, 12:3
↑Tran DD, Saran S, Dittrich-Breiholz O, Williamson AJ, Klebba-Farber S, Koch A, Kracht M, Whetton AD, Tamura T (2013) Transcriptional regulation of immediate-early gene response by THOC5, a member of mRNA export complex, contributes to the M-CSF-induced macrophage differentiation. Cell death & disease 4: e879
↑Saran S, Tran DD, Klebba-Farber S, Moran-Losada P, Wiehlmann L, Koch A, Chopra H, Pabst O, Hoffmann A, Klopfleisch R, Tamura T (2013) THOC5, a member of the mRNA export complex, contributes to processing of a subset of wingless/integrated (Wnt) target mRNAs and integrity of the gut epithelial barrier. BMC Cell Biol 14: 51
↑Griaud, F., Pierce, A., Gonzalez Sanchez, M.B., Scott, M., Abraham, S.A., Holyoake, T.L., Tran, D.D., Tamura, T., and Whetton, A.D. (2013). A pathway from leukemogenic oncogenes and stem cell chemokines to RNA processing via THOC5. Leukemia 27, 932-940.
↑Katahira J, Okuzaki D, Inoue H, Yoneda Y, Maehara K, Ohkawa Y (2013) Human TREX component Thoc5 affects alternative polyadenylation site choice by recruiting mammalian cleavage factor I. Nucleic Acids Research 41: 7060-7072
↑Katahira J, Inoue H, Hurt E, Yoneda Y (2009) Adaptor Aly and co-adaptor Thoc5 function in the Tap-p15-mediated nuclear export of HSP70 mRNA. The EMBO Journal 28: 556-567
↑Ramachandran S., Tran DD., Klebba-Faerber S., Kardinal C., Whetton AD., Tamura T. An ataxia-teleaniectasia-mutated (ATM) kinase mediated response to DNA damage down-regulates the mRNA-binding potential of THOC5. RNA 17(11):1957-66, 2011
↑Guria A., Tran D.D.H,Ramachandran S.,Koch A.,Bounkari O.,Dutta P,Hauser H,Tamura T. Identification of mRNAs that are spliced but not exported to the cytoplasm in the absence of THOC5 in mouse embryo fibroblasts, RNA, 2011 17:00-00.
↑Mancini, A., Niemann-Seyde, S. C., Pankow, R., El Bounkari, O., Klebba-Färber, S., Koch, A., EJaworska, E., Spooncer, E., Gruber, A. D. , Whetton, A. D., Tamura, T. (2010) THOC5/FMIP, an mRNA export TREX complex protein, is essential for hematopoietic primitive cell survival in vivo. BMC Biology 8, 1.
↑Mancini, A., El Bounkari, O., Norrenbrock, A-F., Scherr, M., Schaefer, D., Eder M., Banham, A. H., Pulford, K., Lyne, L., Whetton A. D., and Tamura, T. (2007) FMIP controls the adipocyte lineage commitment of C2C12 cells by down-modulation of C/EBPalpha. Oncogene 26, 1020-1027.
↑Mancini A., Koch A., Whetton A.D., and Tamura T. (2004)The M-CSF receptor substrate and interacting protein FMIP is governed in its subcellular localization by protein kinase C-mediated phosphorylation and thereby potentiates M-CSF-mediated differentiation. Oncogene, 23, 6581-9.
↑Tamura, T., Mancini, A., Joos, H., Koch, A., Hakim, C., Dumanski, J., Weidner, K.M., and Niemann, H. (1999) FMIP, a novel Fms-interacting protein, affects granulocyte/macrophage. Oncogene, 18, 6488-6495.
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↑Carney L, Pierce A, Rijnen M, Gonzalez Sanchez MB, Hamzah HG, Zhang L, Tamura T, Whetton AD (Dec 2008). "THOC5 couples M-CSF receptor signaling to transcription factor expression". Cell Signal. 21 (2): 309–16. doi:10.1016/j.cellsig.2008.10.018. PMID19015024.
↑Pierce A, Carney L, Hamza HG, Griffiths JR, Zhang L, Whetton BA, Gonzalez Sanchez MB, Tamura T, Sternberg D, Whetton AD (May 2008). "THOC5 spliceosome protein: a target for leukaemogenic tyrosine kinases that affects inositol lipid turnover". Br J Haematol. 141 (5): 641–50. doi:10.1111/j.1365-2141.2008.07090.x. PMID18373705.
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