The Xenopus laevis morphogenetic factor, tumorhead, causes defects in polarized growth and cytokinesis in the fission yeast, Schizosaccharomyces pombe

Wu, Cong; Yang, Peirong; Traverso, Edwin E.; Etkin, Laurence D.; Marcus, Stevan

doi:10.1016/j.bbrc.2004.10.046

Cited by 4 publications

(8 citation statements)

References 26 publications

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“…On the contrary, TH overexpression inhibits differentiation possibly by maintaining the cells in a continuous state of proliferation, not allowing them to respond to differentiation factors. More recently, studies in which TH was expressed in the fission yeast Schizosaccharomyces pombe, demonstrated that TH affects the yeast cell growth rate, as well as modulates the cytoskeleton (Wu et al, 2004). Expression of TH in S. pombe results in severe morphological defects, including ovoid, bottleshaped and enlarged cells.…”

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confidence: 99%

Identification of TH-B, a new oligomeric variant of the Xenopus morphogenetic factor, tumorhead

Traverso

Cho

Wu³

et al. 2006

Int. J. Dev. Biol.

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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. KEY WORDS: Xenopus laevis, isoform, cell proliferation, tumorhead, TH-BThe development of germ layers into their tissue derivatives is a complex process involving determination signals that alter the proliferation status of the cells and induce them to follow a specific differentiation program. As the target cells receive these inductive signals, their cell cycle is downregulated, allowing them to differentiate. Therefore, proper coordination between cell proliferation and the processes of determination and differentiation must occur during embryogenesis. This coordination involves bi-directional mechanisms in which cell cycle components play different roles in the regulation of the processes of determination and differentiation and in other instances, factors for determination and differentiation regulate transitions that occur during the cell cycle (Ohnuma et al., 2001). In an analysis of maternally expressed genes that regulate early development in Xenopus laevis, Wu et al. (2001) identified a novel gene named tumorhead (TH). Further experiments indicated that this gene might be a key regulator and/or coordinator of the processes of cell proliferation and differentiation during the development of the ectodermal germ layer. Overexpression of TH results in expansion of the neural plate at the neurula stage and abnormal overgrowths in the head region at the Int. J. Dev. Biol. 50: 423-427 (2006) doi: 10.1387/ijdb.052097et tadpole stage. These alterations in the development of the nervous system are caused by hyper...

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confidence: 99%

Identification of TH-B, a new oligomeric variant of the Xenopus morphogenetic factor, tumorhead

Traverso

Cho

Wu³

et al. 2006

Int. J. Dev. Biol.

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“…These cells appear to have partially lost their ability to polarize cortical F-actin, and have disorganized microtubules. In this study, TH distribution to the fission yeast cell cortex was dependent on Shk1 kinase activity (Wu et al, 2004). Shk1 is the yeast homolog of p21-activated kinase 1 (PAK1), a member of the group I PAK serine/threonine kinases that regulate a broad range of cell signaling networks (for review see, Hofman et al, 2004;Zhao and Manser, 2005;Kumar et al, 2006).…”

Section: Introductionmentioning

confidence: 94%

“…Regulation of TH targeting to specific subcellular compartment is required to control neural development of Xenopus embryos. Our previous studies demonstrated that expressed TH in S. pombe cells distributes to the cell cortex and septum and that its cortical localization is under the control of Shk1, the S. pombe p21 activated kinase homolog (PAK) (Wu et al, 2004). In order to study a potential relationship between TH and X-PAK1 signaling pathways during neurulation in Xenopus, we first wanted to ensure that the endogenous PAK1 kinase and TH are expressed in the same territories during neural development.…”

Section: Endogenous X-pak1 Is Expressed In the Neural Field At Neurulmentioning

confidence: 99%

“…Thus, nuclear TH and cytoplasmic/cortical TH are likely to interact with different partners, and the understanding of the regulation of TH shuttling would help to identify the signaling cascade to which it belongs. In fission yeast, TH binding to the cell cortex is dependent on the kinase activity of S. pombe p21activated kinase, Shk1 (PAK1) (Wu et al, 2004). Mammalian PAKs also regulate the distribution of a number of target genes, allowing their localized activity.…”

Section: Th Activity Depends On Its Subcellular Distribution and Th Lmentioning

confidence: 99%

“…We observed that the elongated shape of neural tube cells was lost in embryos lacking TH, indicating that TH might control cytoskeleton rearrangements. This hypothesis is strengthened by the observation that expression of TH in S. pombe cells induces severe morphological defects (Wu et al, 2004) that are characterized by ovoid, enlarged and sometimes mutiseptated cells. These cells appear to have partially lost their ability to polarize cortical F-actin, and have disorganized microtubules.…”

Section: Introductionmentioning

confidence: 98%

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Tumorhead distribution to cytoplasmic membrane of neural plate cells is positively regulated by Xenopus p21-activated kinase 1 (X-PAK1)

Delsert

Faure

et al. 2007

Developmental Biology

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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.

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Current awareness on yeast

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In order to keep subscribers up‐to‐date with the latest developments in their field, this current awareness service is provided by John Wiley & Sons and contains newly‐published material on yeasts. Each bibliography is divided into 10 sections. 1 Books, Reviews & Symposia; 2 General; 3 Biochemistry; 4 Biotechnology; 5 Cell Biology; 6 Gene Expression; 7 Genetics; 8 Physiology; 9 Medical Mycology; 10 Recombinant DNA Technology. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted. (5 weeks journals ‐ search completed 12th. Jan. 2005)

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The Xenopus laevis morphogenetic factor, tumorhead, causes defects in polarized growth and cytokinesis in the fission yeast, Schizosaccharomyces pombe

Cited by 4 publications

References 26 publications

Identification of TH-B, a new oligomeric variant of the Xenopus morphogenetic factor, tumorhead

Identification of TH-B, a new oligomeric variant of the Xenopus morphogenetic factor, tumorhead

Tumorhead distribution to cytoplasmic membrane of neural plate cells is positively regulated by Xenopus p21-activated kinase 1 (X-PAK1)

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