7 research outputs found
Wnt target genes identified by DNA microarrays in immature CD34+ thymocytes regulate proliferation and cell adhesion
The thymus is seeded by very small numbers of progenitor cells that
undergo massive proliferation before differentiation and rearrangement of
TCR genes occurs. Various signals mediate proliferation and
differentiation of these cells, including Wnt signals. Wnt signals induce
the interaction of the cytoplasmic cofactor beta-catenin with nuclear T
cell factor (TCF) transcription factors. We identified target genes of the
Wnt/beta-catenin/TCF pathway in the most immature (CD4-CD8-CD34+)
thymocytes using Affymetrix DNA microarrays in combination with three
different functional assays for in vitro induction of Wnt signaling. A
relatively small number (approximately 30) of genes changed expression,
including several proliferation-inducing transcription factors such as
c-fos and c-jun, protein phosphatases, and adhesion molecules, but no
genes involved in differentiation to mature T cell stages. The adhesion
molecules likely confine the proliferating immature thymocytes to the
appropriate anatomical sites in the thymus. For several of these target
genes, we validated that they are true Wnt/beta-catenin/TCF target genes
using real-time quantitative PCR and reporter gene assays. The same core
set of genes was repressed in Tcf-1-null mice, explaining the block in
early thymocyte development in these mice. In conclusion, Wnt signals
mediate proliferation and cell adhesion, but not differentiation of the
immature thymic progenitor pool
The von Hippel-Lindau tumour suppressor interacts with microtubules through kinesin-2
Synthesis and maintenance of primary cilia are regulated by the von Hippel-Lindau (VHL) tumour suppressor protein. Recent studies indicate that this regulation is linked to microtubule-dependent functions of pVHL such as orienting microtubule growth and increasing plus-end microtubule stability, however little is known how this occurs. We have identified the kinesin-2 motor complex, known to regulate cilia, as a novel and endogenous pVHL binding partner. The interaction with kinesin-2 facilitates pVHL binding to microtubules. These data suggest that microtubule-dependent functions of pVHL are influenced by kinesin-2
The von Hippel–Lindau tumour suppressor interacts with microtubules through kinesin-2
AbstractSynthesis and maintenance of primary cilia are regulated by the von Hippel–Lindau (VHL) tumour suppressor protein. Recent studies indicate that this regulation is linked to microtubule-dependent functions of pVHL such as orienting microtubule growth and increasing plus-end microtubule stability, however little is known how this occurs. We have identified the kinesin-2 motor complex, known to regulate cilia, as a novel and endogenous pVHL binding partner. The interaction with kinesin-2 facilitates pVHL binding to microtubules. These data suggest that microtubule-dependent functions of pVHL are influenced by kinesin-2