| Structural highlights
Disease
[TCL1A_HUMAN] Note=Chromosomal aberrations activating TCL1A are found in chronic T-cell leukemias (T-CLL). Translocation t(14;14)(q11;q32); translocation t(7;14)(q35;q32); inversion inv(14)(q11;q32) that involves the T-cell receptor alpha/delta loci.
Function
[TCL1A_HUMAN] Enhances the phosphorylation and activation of AKT1, AKT2 and AKT3. Promotes nuclear translocation of AKT1. Enhances cell proliferation, stabilizes mitochondrial membrane potential and promotes cell survival.[1] [2] [3] [4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
BACKGROUND: Chromosome rearrangements are frequently involved in the generation of hematopoietic tumors. One type of T-cell leukemia, T-cell prolymphocytic leukemia, is consistently associated with chromosome rearrangements characterized by the juxtaposition of the TCRA locus on chromosome 14q11 and either the TCL1 gene on 14q32.1 or the MTCP1 gene on Xq28. The TCL1 gene is preferentially expressed in cells of early lymphoid lineage; its product is a 14 kDa protein (p14TCL1), expressed in the cytoplasm. p14TCL1 has strong sequence similarity with one product of the MTCP1 gene, p13MTCP1 (41% identical and 61% similar). The functions of the TCL1 and MTCP1 genes are not known yet. They have no sequence similarity to any other published sequence, including those of well-documented oncogene families responsible for leukemia. In order to gain a more fundamental insight into the role of this particular class of oncogenes, we have determined the three-dimensional structure of p14TCL1. RESULTS: The crystal structure of p14TCL1 has been determined at 2.5 A resolution. The structure was solved by molecular replacement using the solution structure of p13MTCP1, revealing p14TCL1 to be an all-beta protein consisting of an eight-stranded antiparallel beta barrel with a novel topology. The barrel consists of two four-stranded beta-meander motifs, related by a twofold axis and connected by a long loop. This internal pseudo-twofold symmetry was not expected on basis of the sequence alone, but structure-based sequence analysis of the two motifs shows that they are related. The structures of p13MTCP1 and p14TCL1 are very similar, diverging only in regions that are either flexible and/or involved in crystal packing. p14TCL1 forms a tight crystallographic dimer, probably corresponding to the 28 kDa species identified in solution by gel filtration experiments. CONCLUSIONS: Structural similarities between p14TCL1 and p13MTCP1 suggest that their (unknown) function may be analogous. This is confirmed by the fact that these proteins are implicated in analogous diseases. Their structure does not show similarity to other oncoproteins of known structure, confirming their classification as a novel class of oncoproteins.
Crystal structure of p14TCL1, an oncogene product involved in T-cell prolymphocytic leukemia, reveals a novel beta-barrel topology.,Hoh F, Yang YS, Guignard L, Padilla A, Stern MH, Lhoste JM, van Tilbeurgh H Structure. 1998 Feb 15;6(2):147-55. PMID:9519406[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Laine J, Kunstle G, Obata T, Sha M, Noguchi M. The protooncogene TCL1 is an Akt kinase coactivator. Mol Cell. 2000 Aug;6(2):395-407. PMID:10983986
- ↑ Pekarsky Y, Koval A, Hallas C, Bichi R, Tresini M, Malstrom S, Russo G, Tsichlis P, Croce CM. Tcl1 enhances Akt kinase activity and mediates its nuclear translocation. Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3028-33. PMID:10716693 doi:10.1073/pnas.040557697
- ↑ Laine J, Kunstle G, Obata T, Noguchi M. Differential regulation of Akt kinase isoforms by the members of the TCL1 oncogene family. J Biol Chem. 2002 Feb 1;277(5):3743-51. Epub 2001 Nov 13. PMID:11707444 doi:10.1074/jbc.M107069200
- ↑ Kunstle G, Laine J, Pierron G, Kagami Si S, Nakajima H, Hoh F, Roumestand C, Stern MH, Noguchi M. Identification of Akt association and oligomerization domains of the Akt kinase coactivator TCL1. Mol Cell Biol. 2002 Mar;22(5):1513-25. PMID:11839817
- ↑ Hoh F, Yang YS, Guignard L, Padilla A, Stern MH, Lhoste JM, van Tilbeurgh H. Crystal structure of p14TCL1, an oncogene product involved in T-cell prolymphocytic leukemia, reveals a novel beta-barrel topology. Structure. 1998 Feb 15;6(2):147-55. PMID:9519406
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