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Implication of the VRK1 chromatin kinase in the signaling responses to DNA damage: a therapeutic target?

-Universidad de Salamanca , 37007 Salamanca , Spain 2 Pedro A. Lazo DNA damage causes a local distortion of chromatin that triggers the sequential processes that participate in specific DNA repair mechanisms

VRK1 and AURKB form a complex that cross inhibit their kinase activity and the phosphorylation of histone H3 in the progression of mitosis

Abbreviations VRK1 Vaccinia-related kinase 1 AURKB Aurora kinase B ACA Anti-centromere antibody H3 Histone 3 CPC Chromosome passenger complex 3 Pedro A. Lazo Regulation of cell division requires the integration

Downregulation of VRK1 by p53 in Response to DNA Damage Is Mediated by the Autophagic Pathway

Human VRK1 induces a stabilization and accumulation of p53 by specific phosphorylation in Thr18. This p53 accumulation is reversed by its downregulation mediated by Hdm2, requiring a dephosphorylated p53 and therefore also needs the removal of VRK1 as stabilizer. This process requires export of VRK1 to the cytosol and is inhibited by leptomycin B. We have identified that...

JC virus in the pathogenesis of colorectal cancer, an etiological agent or another component in a multistep process?

Tatiana R Coelho Luis Almeida Pedro A Lazo 0 0 Experimental Therapeutics and Translational Oncology Program, Instituto de Biologia Molecular y Celular del Cancer, Consejo Superior de Investigaciones

Differential Inhibitor Sensitivity between Human Kinases VRK1 and VRK2

Human vaccinia-related kinases (VRK1 and VRK2) are atypical active Ser-Thr kinases implicated in control of cell cycle entry, apoptosis and autophagy, and affect signalling by mitogen activated protein kinases (MAPK). The specific structural differences in VRK catalytic sites make them suitable candidates for development of specific inhibitors. In this work we have determined the...

The C/H3 Domain of p300 Is Required to Protect VRK1 and VRK2 from their Downregulation Induced by p53

BackgroundThe vaccinia-related kinase 1 (VRK1) protein, an activator of p53, can be proteolytically downregulated by an indirect mechanism, which requires p53-dependent transcription.Principal FindingsIn this work we have biochemically characterized the contribution of several p53 transcriptional cofactors with acetyl transferase activity to the induction of VRK1 downregulation...

Human VRK1 Is an Early Response Gene and Its Loss Causes a Block in Cell Cycle Progression

BackgroundIn mammalian cells regulatory proteins controlling the cell cycle are necessary due to the requirements of living in a heterogeneous environment of cell-interactions and growth factors. VRK1 is a novel serine-threonine kinase that phosphorylates several transcription factors and is associated with proliferation phenotypes.Methodology/Principal FindingsIn this report...

Modulation of Interleukin-1 Transcriptional Response by the Interaction between VRK2 and the JIP1 Scaffold Protein

BackgroundCellular biological responses to specific stimulation are determined by a balance among signaling pathways. Protein interactions are likely to modulate these pathways. Vaccinia-related kinase-2 (VRK2) is a novel human kinase that can modulate different signaling pathways.Principal FindingsWe report that in vivo, the activity of JIP1-JNK complexes is downregulated by...

The SRY-HMG box gene, SOX4, is a target of gene amplification at chromosome 6p in lung cancer†

Pedro A. Lazo 0 Montse Sanchez-Cespedes 2 0 Programa de Oncologia Translacional, Instituto de Biologia Molecular y Celular del Cancer (CIC)-Consejo Superior de Investigaciones Cientificas (CSIC