High impact information on ASK1

• Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways [1].
• Overexpression of ASK1 induced apoptotic cell death, and ASK1 was activated in cells treated with tumor necrosis factor-alpha (TNF-alpha) [1].
• Microtubules are required for Ask1 binding to kinetochores, and are partially required to maintain its association [2].
• Here we describe the isolation of a novel and conserved essential gene, ASK1, from Saccharomyces cerevisiae involved in this process. ask1 mutants display either G(2)/M arrest or segregation of DNA masses without the separation of sister chromatids, resulting in massive nondisjunction and broken spindles [2].
• A yeast two-hybrid screening identified a serine/threonine protein phosphatase 5 (PP5) as a binding partner of ASK1 [3].

Biological context of ASK1

• Ask1 localizes along mitotic spindles and to kinetochores, and cross-links to centromeric DNA [2].
• Cdc14 promotes localization of microtubule-stabilizing proteins to the anaphase spindle, and dephosphorylation of the kinetochore component Ask1 contributes to both the silencing of microtubule turnover and successful anaphase A [4].
• Negative feedback regulation of ASK1 by protein phosphatase 5 (PP5) in response to oxidative stress [3].
• ASK1 associates with troponin T and induces troponin T phosphorylation and contractile dysfunction in cardiomyocytes [5].
• Akt/protein kinase B is a major cell survival pathway through phosphorylation of proapoptotic proteins Bad and Bax and of additional apoptotic pathways linked to Forkhead proteins glycogen synthase kinase-3beta and ASK1 [6].

Anatomical context of ASK1

• Furthermore, mGSTM1-1 suppressed stress-stimulated ASK1 activity in cultured cells. mGSTM1-1 also blocked ASK1 oligomerization [7].

Associations of ASK1 with chemical compounds

• The interaction between PP5 and ASK1 was induced by H(2)O(2) treatment and was followed by the decrease in ASK1 activity [3].
• Direct Interaction and Reciprocal Regulation between ASK1 and Calcineurin-NFAT Control Cardiomyocyte Death and Growth [8].
• The ASK1 inhibition by mGSTM1-1 occurred independently of the glutathione-conjugating activity of mGSTM1-1 [7].

Other interactions of ASK1

• Constitutive PKA activity caused by mutation of the negative regulator BCY1 is toxic to DASH mutants such as ask1 and dam1 [9].
• We propose that Hsk3 acts to incorporate Ask1 into the DASH complex [9].

Analytical, diagnostic and therapeutic context of ASK1

• Yeast two-hybrid assay and immunoprecipitation experiments demonstrated that GID2 is a component of the SCF complex through an interaction with a rice ASK1 homolog, OsSkp15 [10].
• Coimmunoprecipitation studies demonstrated that CDC25A physically associates with ASK1 in mammalian cells, and immunocytochemistry with confocal laser-scanning microscopy showed that these two proteins colocalize in the cytoplasm [11].
• We have recently identified ASK1-interacting protein (AIP1) as novel signal transducer in TNFalpha-induced ASK1 activation by facilitating dissociation of ASK1 from its inhibitor 14-3-3 [12].

References