TCL1 and TCL1b genes on human chromosome 14q23.1 are activated in T cell
leukemias by translocations and inversions at 14q32.1, juxtaposing them to
regulatory elements of T cell receptor genes.
By searching an EST database for sequences
homologous to TCL1A and MTCP1 (OMIM 300116), a member of the TCL1 gene family that
is located on Xq28 and is activated in rare cases of mature T-cell leukemia with a
t(X;14) translocation,TCL1B was isolated.
General function
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Cellular localization
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Ovarian function
Oogenesis, Early embryo development
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Oocyte Factors Suppress Mitochondrial Polynucleotide Phosphorylase to Remodel the Metabolome and Enhance Reprogramming. Khaw SL et al. (2015) Oocyte factors not only drive somatic cell nuclear transfer reprogramming but also augment the efficiency and quality of induced pluripotent stem cell (iPSC) reprogramming. Here, we show that the oocyte-enriched factors Tcl1 and Tcl1b1 significantly enhance reprogramming efficiency. Clonal analysis of pluripotency biomarkers further show that the Tcl1 oocyte factors improve the quality of reprogramming. Mechanistically, we find that the enhancement effect of Tcl1b1 depends on Akt, one of its putative targets. In contrast, Tcl1 suppresses the mitochondrial polynucleotide phosphorylase (PnPase) to promote reprogramming. Knockdown of PnPase rescues the inhibitory effect from Tcl1 knockdown during reprogramming, whereas PnPase overexpression abrogates the enhancement from Tcl1 overexpression. We further demonstrate that Tcl1 suppresses PnPase's mitochondrial localization to inhibit mitochondrial biogenesis and oxidation phosphorylation, thus remodeling the metabolome. Hence, we identified the Tcl1-PnPase pathway as a critical mitochondrial switch during reprogramming.//////////////////
Expression regulated by
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Ovarian localization
Oocyte
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Hallas C, et al 1999 reported genomic analysis of human and mouse TCL1 loci reveals a
complex of tightly clustered genes.
In
addition to TCL1 and TCL1b, the human locus contains two additional genes,
TCL1-neighboring genes (TNG) 1 and 2, encoding proteins of 141 and 110 aa,
respectively. Both genes show no homology to any known genes, but their
expression profiles are very similar to those of TCL1 and TCL1b. TNG1 and
TNG2 also are activated in T cell leukemias with rearrangements at 14q32.1. To
aid in the development of a mouse model the authors also have characterized the murine
Tcl1 locus and found five genes homologous to human TCL1b. Tcl1b1-Tcl1b5
proteins range from 117 to 123 aa and are 65-80% similar, but they show only a
30-40% similarity to human TCL1b. All five mouse Tcl1b and murine Tcl1
mRNAs are abundant in mouse oocytes and two-cell embryos but rare in various
adult tissues and lymphoid cell lines. These data suggest a similar or
complementary function of these proteins in early embryogenesis.