Chapter 12 The Genesis of Behaviorally Modern Homo sapiens

This book is a “big history” of the evidence regarding how we came to be. It briefly explores philosophical thought and how our past might affect our future. The text summarizes different perspectives, including the strengths and weaknesses of each. The genesis of our planet is explored, especially the circumstances that must exist for complex life to arise. This brief journey highlights the history of life, the emergence of simple lifeforms, and the evolution of complex creatures, including humans. The book concludes with a discussion of why other humanoids went extinct while our species achieved dominance. The author speculates on potentialities awaiting humankind and our planet

The cytoplasmic zinc finger protein ZPR1 accumulates in the nucleolus of proliferating cells

The zinc finger protein ZPR1 translocates from the cytoplasm to the nucleus after treatment of cells with mitogens. The function of nuclear ZPR1 has not been defined. Here we demonstrate that ZPR1 accumulates in the nucleolus of proliferating cells. The role of ZPR1 was examined using a gene disruption strategy. Cells lacking ZPR1 are not viable. Biochemical analysis demonstrated that the loss of ZPR1 caused disruption of nucleolar function, including preribosomal RNA expression. These data establish ZPR1 as an essential protein that is required for normal nucleolar function in proliferating cells

Regulation of RKIP Function by Helicobacter pylori in Gastric Cancer

Helicobacter pylori (H. pylori) is a gram-negative, spiral-shaped bacterium that infects more than half of the world’s population and is a major cause of gastric adenocarcinoma. The mechanisms that link H. pylori infection to gastric carcinogenesis are not well understood. In the present study, we report that the Raf-kinase inhibitor protein (RKIP) has a role in the induction of apoptosis by H. pylori in gastric epithelial cells. Western blot and luciferase transcription reporter assays demonstrate that the pathogenicity island of H. pylori rapidly phosphorylates RKIP, which then localizes to the nucleus where it activates its own transcription and induces apoptosis. Forced overexpression of RKIP enhances apoptosis in H. pylori-infected cells, whereas RKIP RNA inhibition suppresses the induction of apoptosis by H. pylori infection. While inducing the phosphorylation of RKIP, H. pylori simultaneously targets non-phosphorylated RKIP for proteasome-mediated degradation. The increase in RKIP transcription and phosphorylation is abrogated by mutating RKIP serine 153 to valine, demonstrating that regulation of RKIP activity by H. pylori is dependent upon RKIP’s S153 residue. In addition, H. pylori infection increases the expression of Snail, a transcriptional repressor of RKIP. Our results suggest that H. pylori utilizes a tumor suppressor protein, RKIP, to promote apoptosis in gastric cancer cells

A Most Improbable Story

This book is a “big history” of the evidence regarding how we came to be. It briefly explores philosophical thought and how our past might affect our future. The text summarizes different perspectives, including the strengths and weaknesses of each. The genesis of our planet is explored, especially the circumstances that must exist for complex life to arise. This brief journey highlights the history of life, the emergence of simple lifeforms, and the evolution of complex creatures, including humans. The book concludes with a discussion of why other humanoids went extinct while our species achieved dominance. The author speculates on potentialities awaiting humankind and our planet

A Most Improbable Story

This book is a “big history” of the evidence regarding how we came to be. It briefly explores philosophical thought and how our past might affect our future. The text summarizes different perspectives, including the strengths and weaknesses of each. The genesis of our planet is explored, especially the circumstances that must exist for complex life to arise. This brief journey highlights the history of life, the emergence of simple lifeforms, and the evolution of complex creatures, including humans. The book concludes with a discussion of why other humanoids went extinct while our species achieved dominance. The author speculates on potentialities awaiting humankind and our planet

Chapter 12 The Genesis of Behaviorally Modern Homo sapiens

This book is a “big history” of the evidence regarding how we came to be. It briefly explores philosophical thought and how our past might affect our future. The text summarizes different perspectives, including the strengths and weaknesses of each. The genesis of our planet is explored, especially the circumstances that must exist for complex life to arise. This brief journey highlights the history of life, the emergence of simple lifeforms, and the evolution of complex creatures, including humans. The book concludes with a discussion of why other humanoids went extinct while our species achieved dominance. The author speculates on potentialities awaiting humankind and our planet

Mutational removal of the major site of serine phosphorylation of the epidermal growth factor receptor causes potentiation of signal transduction: role of receptor down-regulation

The major site of epidermal growth factor receptor (EGF-R) serine phosphorylation is located within the COOH-terminal domain of the receptor at Ser1046/7. We have previously demonstrated that this phosphorylation site accounts for the acute desensitization of the EGF-R observed in EGF-treated cells. Here we show that the mutational removal of this negative regulatory phosphorylation site causes potentiation of signal transduction by the EGF-R. This potentiation can be accounted for in part by a block in the EGF-stimulated down-regulation of the EGF-R. These data indicate that the SER1046/7 phosphorylation site may have a regulatory role during long term incubation of cells with mitogenic concentrations of EGF

Increased oncogenic potential of ErbB is associated with the loss of a COOH-terminal domain serine phosphorylation site

The erbB oncogene encodes an altered form of the epidermal growth factor (EGF) receptor that lacks the extracellular ligand binding domain. This oncogene is exclusively leukemogenic. However, an increase in oncogenic potential and a broadening of the tissue specificity of tumor formation occurs after retroviral transduction of erbB. The increased oncogenic potential correlates with structural alterations within the erbB gene. One common event is the deletion of a serine phosphorylation site located within the COOH-terminal domain. This site of phosphorylation has been demonstrated to be required for EGF-induced desensitization of signaling by the EGF receptor (Countaway, J. L., Nairn, A. C., and Davis, R.J. (1992) J. Biol. Chem. 267, 1129-1140). Here we show that the mutation of erbB at this negative regulatory serine phosphorylation site causes fibroblast transformation in vitro and is associated with an increased oncogenic potential in vivo