Chuan-Fen Wu

University of Texas MD Anderson Cancer Center, Houston, TX, United States

Are you Chuan-Fen Wu?

Claim your profile

Publications (4)13.99 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The Xenopus laevis tumorhead (TH) protein, a positive regulator of cell proliferation during embryogenesis, shuttles from the cell periphery into the nucleus during embryogenesis. In these studies, we performed a detailed analysis of TH's subcellular localization pattern to characterize its dynamic behavior. We found that TH exhibits distinct patterns of localization in different germ layers. At the blastula stage, TH is present in the apical cell periphery of prospective mesodermal and ectodermal cells. At the gastrula stage, TH is distributed throughout the entire cytoplasm of prospective mesodermal and ectodermal cells, whereas it shows nuclear localization in presumptive endodermal cells. TH moves into the nucleus of mesodermal and ectodermal cells during the neurula and early tailbud stages. To understand if TH is regulated by changes in its subcellular localization, we used a TH mutant containing signals for farnesylation and palmitoylation to tether the protein to the plasma membrane. Ubiquitous overexpression of this mutant causes embryonic lethality at the early gastrula transition. Further examination using TUNEL assays indicated that wild-type TH overexpression induces apoptosis during gastrulation, and that this effect is exacerbated by the overexpression of the membrane-bound TH mutant. Taken together, our results suggest that changes in the sub-cellular localization of the TH protein are important for its function because blocking the nuclear translocation of overexpressed TH increases apoptosis and causes embryos to die. Our data also suggest that TH plays a role outside the nucleus when it is present at the cell periphery.
    Differentiation 01/2008; 75(10):947-56. · 2.86 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Tumorhead (TH) regulates neural plate cell proliferation during Xenopus early development, and gain or loss of function prevents neural differentiation. TH shuttles between the nuclear and cytoplasmic/cortical cell compartments in embryonic cells. In this study, we show that subcellular distribution of TH is important for its functions. Targeting TH to the cell cortex/membrane potentiates a TH gain of function phenotype and results in neural plate expansion and inhibition of neuronal differentiation. We have found that TH subcellular localization is regulated, and that its shuttling between the nucleus and the cell cortex/cytoplasm is controlled by the catalytic activity of p21-activated kinase, X-PAK1. The phenotypes of embryos that lack, or have excess, X-PAK1 activity mimic the phenotypes induced by loss or gain of TH functions, respectively. We provide evidence that X-PAK1 is an upstream regulator of TH and discuss potential functions of TH at the cell cortex/cytoplasmic membrane and in the nucleus.
    Developmental Biology 09/2007; 308(1):169-86. · 3.87 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The Xenopus laevis gene tumorhead (TH) is a regulator of cell proliferation of the ectodermal germ layer during embryonic development. TH overexpression results in increased cell proliferation within the developing ectoderm, causing an expansion of the neural plate. Conversely, loss of TH function results in inhibition of proliferation of ectodermal cells. Embryos with altered levels of TH protein are unable to express neural differentiation markers, indicating that the effect of TH in proliferation is linked with differentiation in the nervous system. To date, the molecular mechanism by which TH affects cell proliferation during embryogenesis is unknown. We have utilized the yeast two-hybrid system to identify protein partners of TH that could lead us to define the mechanism or pathway through which TH functions. Using this assay we have identified a new variant of TH designated TH-B, as a potential protein partner of the original TH, now referred to as TH-A. The sequence for TH-B was found to be 85% identical at the amino acid level to the TH-A sequence. Further characterization of the TH-B variant using RT-PCR indicates that it is expressed ubiquitously throughout development from early cleavage stages until at least the tadpole stage. TH-B association with TH-A was confirmed in co-immnoprecipitation studies in Xenopus, indicating that the two variants may function as an oligomer in vivo. These studies reveal the presence of an isoform of TH that may possess novel functional capabilities.
    The International Journal of Developmental Biology 02/2006; 50(4):423-7. · 2.61 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A 95-kDa protein in Xenopus oocytes, Xp95, was shown to be phosphorylated from the first through the second meiotic divisions during progesterone-induced oocyte maturation. Xp95 was purified and cloned. The Xp95 protein sequence exhibited homology to mouse Rhophilin, budding yeast Bro1, and AspergillusPalA, all of which are implicated in signal transduction. It also contained three conserved features including seven conserved tyrosines, a phosphorylation consensus sequence for the Src family of tyrosine kinases, and a proline-rich domain near the C terminus that contains multiple SH3 domain-binding motifs. We showed the following: 1) that both Xp95 isolated from Xenopus oocytes and a synthetic peptide containing the Src phosphorylation consensus sequence of Xp95 were phosphorylated in vitro by Src kinase and to a lesser extent by Fyn kinase; 2) Xp95 from Xenopus oocytes or eggs was recognized by an anti-phosphotyrosine antibody, and the relative abundance of tyrosine-phosphorylated Xp95 increased during oocyte maturation; and 3) microinjection of deregulated Src mRNA intoXenopus oocytes increased the abundance of tyrosine-phosphorylated Xp95. These results suggest that Xp95 is an element in a tyrosine kinase signaling pathway that may be involved in progesterone-induced Xenopus oocyte maturation.
    Journal of Biological Chemistry 02/1999; 274(9):5522-5531. · 4.65 Impact Factor