Tweeny R. Kau

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The PI3K/PTEN/Akt signal transduction pathway plays a key role in many tumors. Downstream targets of this pathway include the Forkhead family of transcription factors (FOXO1a, FOXO3a, FOXO4). In PTEN null cells, FOXO1a is inactivated by PI3K-dependent phosphorylation and mislocalization to the cytoplasm, yet still undergoes nucleocytoplasmic shuttling.(More)
Nuclear-cytoplasmic transport, which occurs through special structures called nuclear pores, is an important aspect of normal cell function, and defects in this process have been detected in many different types of cancer cells. These defects can occur in the signal-transduction pathways that regulate the transfer of factors such as p53 and β-catenin in and(More)
Phosphatidylinositol-3-kinase (PI3K), and its downstream effector Akt, or protein kinase Balpha (PKBalpha), play a major regulatory role in control of apoptosis, proliferation, and angiogenesis. PI3K and Akt are amplified or overexpressed in a number of malignancies, including sarcomas, ovarian cancer, multiple myeloma, and melanoma. This pathway regulates(More)
A small collection of marine natural product extracts was screened for compounds that would compensate lost tumor suppressor functionality in PTEN-deficient cells. From the most active extract, the previously unreported bromotyrosine derivative, psammaplysene A (1), was identified. Psammaplysene A compensates for PTEN loss by relocalizing the transcription(More)
After chromosome replication, the intertwined sister chromatids are disentangled by topoisomerases. The integrity of this process is monitored by the chromatid decatenation checkpoint. Here, we describe small molecule modulators of the human chromatid decatenation checkpoint identified using a cell-based, chemical genetic modifier screen. Similar to(More)
Phosphatidylinositol-3-kinase (PI3K), and its downstream effector Akt, or protein kinase Bα (PKBα), play a major regulatory role in control of apoptosis, proliferation, and angiogenesis. PI3K and Akt are amplified or overexpressed in a number of malignancies, including sarcomas, ovarian cancer, multiple myeloma, and melanoma. This pathway regulates(More)
Solenopsin, the alkaloidal component of the fire ant (Solenopsis invicta), is a naturally occurring inhibitor of phosphatidylinositol-3-kinase signaling and angiogenesis Jack L. Arbiser,1 Tweeny Kau,2 Martha Konar,3 Krishna Narra,4 Ramani Ramchandran,3 Scott A. Summers,4 Chris J. Vlahos,5 Keqiang Ye,6 Betsy N. Perry,1 William Matter,5 Anthony Fischl,5 James(More)
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