Story Summary: Chemotherapy: Imatinib is Abl to preserve fertilityPharmaceutical inhibition of a c-Abl-TAp63 signaling pathway protects female mice from chemotherapy-induced infertility. In Nature Medicine, Stefania Gonfloni et al. now identify a pro-apoptotic c-Abl-TAp63 pathway that is induced by chemotherapy in oocytes. Indeed, cisplatin treatment caused a decrease in primordial and primary follicles in mouse ovaries. A remaining question is whether inhibition of this pathway will affect tumor regression, especially given that p63 has a known role in cell death, and that activation of c-Abl has been shown to induce apoptosis in tumors. It will be important to determine if imatinib treatment during chemotherapy affects tumor regression, and if other DNA-damaging agents can also induce c-Abl-TAp63 activation. Emily J. ChenetteSignaling GatewayProtein trafficking: PTEN hitches a ride on myosinVAn interaction between PTEN and myosinV regulates PTEN function and neuronal soma size. The lipid phosphatase PTEN antagonizes PI(3)K (phosphoinositide 3-kinase) activity by dephosphorylating phosphatidylinositol (3,4,5)-trisphosphate (PIP3) to form PI(4,5)P2. PTEN is active at the plasma membrane, where the PI(3)K-generated pools of PIP3 reside, but the mechanisms governing PTEN membrane translocation are not well understood. Overexpression of the myosinVa globular domain (MVag), which competes with full-length myosinV proteins for binding to PTEN, increased soma size of murine hippocampal neurons in vivo — a phenotype reminiscent of hippocampal neurons in PTEN-null mice. Eickholt and colleagues found that constitutively active GSK3b reduced S6 phosphorylation and soma size, whereas expression of either MVag or a phosphatase-dead myristoylated PTEN mutant increased soma size and S6 phosphorylation. Intriguingly, GSK3b is known to be inhibited by PI(3)K signaling, which suggests that the PTEN-myosinV interaction might be regulated by a positive feedback loop. Emily J. ChenetteSignaling Gatewayb-catenin regulation: TNKS for nothingA small-molecule inhibitor of tankyrase promotes the degradation of b-catenin by stabilizing axin protein levels. XAV939 binds to and inhibits the poly(ADP-ribose) polymerases tankyrase 1 (TNKS1) and TNKS2. Remarkably, a role for TNKS in Wnt pathway signaling had not previously been appreciated. Emily J. ChenetteSignaling GatewayFeatured articles: October 2009Each week we showcase a hot new cell signaling article from a Nature Publishing Group journal….Read the Full Story

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