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Papers by Wan Leong

Research paper thumbnail of Runx1 Phosphorylation by Src Increases Trans-Activation via Augmented Stability, Reduced HDAC Binding, and Increased DNA Affinity, and Activated Runx1 Favors Granulopoiesis

The Journal of biological chemistry, Jan 23, 2015

Src phosphorylates Runx1 on one central and four C-terminal tyrosines. We find that activated Src... more Src phosphorylates Runx1 on one central and four C-terminal tyrosines. We find that activated Src synergizes with Runx1 to activate a Runx1 luciferase reporter. Mutation of the four Runx1 C-terminal tyrosines to aspartate or glutamate to mimic phosphorylation increases trans-activation of the reporter in 293T cells and allows induction of Cebpa or Pu.1 mRNAs in 32Dcl3 myeloid cells, whereas mutation of these residues to phenylalanine to prevent phosphorylation obviates these effects. Three mechanisms contribute to increased Runx1 activity upon tyrosine modification - increased stability, reduced HDAC interaction, and increased DNA-binding. Mutation of the five modified Runx1 tyrosines to aspartate markedly reduced co-immunoprecipitation with HDAC1 and HDAC3, markedly increased stability in cycloheximide or in the presence of co-expressed Cdh1, an E3 ubiquitin ligase coactivator, with reduced ubiquitination, and allowed DNA-binding in gel shift assay similar to wild-type Runx1. In co...

Research paper thumbnail of LOMA: A fast method to generate efficient tagged-random primers despite amplification bias of random PCR on pathogens

BMC Bioinformatics, 2008

Background: Pathogen detection using DNA microarrays has the potential to become a fast and compr... more Background: Pathogen detection using DNA microarrays has the potential to become a fast and comprehensive diagnostics tool. However, since pathogen detection chips currently utilize random primers rather than specific primers for the RT-PCR step, bias inherent in random PCR amplification becomes a serious problem that causes large inaccuracies in hybridization signals.

Research paper thumbnail of RCP is a human breast cancer–promoting gene with Ras-activating function

Journal of Clinical Investigation, 2009

Aggressive forms of cancer are often defined by recurrent chromosomal alterations, yet in most ca... more Aggressive forms of cancer are often defined by recurrent chromosomal alterations, yet in most cases, the causal or contributing genetic components remain poorly understood. Here, we utilized microarray informatics to identify candidate oncogenes potentially contributing to aggressive breast cancer behavior. We identified the Rab-coupling protein RCP (also known as RAB11FIP1), which is located at a chromosomal region frequently amplified in breast cancer (8p11-12) as a potential candidate. Overexpression of RCP in

Research paper thumbnail of Runx1 Phosphorylation by Src Increases Trans-Activation via Augmented Stability, Reduced HDAC Binding, and Increased DNA Affinity, and Activated Runx1 Favors Granulopoiesis

The Journal of biological chemistry, Jan 23, 2015

Src phosphorylates Runx1 on one central and four C-terminal tyrosines. We find that activated Src... more Src phosphorylates Runx1 on one central and four C-terminal tyrosines. We find that activated Src synergizes with Runx1 to activate a Runx1 luciferase reporter. Mutation of the four Runx1 C-terminal tyrosines to aspartate or glutamate to mimic phosphorylation increases trans-activation of the reporter in 293T cells and allows induction of Cebpa or Pu.1 mRNAs in 32Dcl3 myeloid cells, whereas mutation of these residues to phenylalanine to prevent phosphorylation obviates these effects. Three mechanisms contribute to increased Runx1 activity upon tyrosine modification - increased stability, reduced HDAC interaction, and increased DNA-binding. Mutation of the five modified Runx1 tyrosines to aspartate markedly reduced co-immunoprecipitation with HDAC1 and HDAC3, markedly increased stability in cycloheximide or in the presence of co-expressed Cdh1, an E3 ubiquitin ligase coactivator, with reduced ubiquitination, and allowed DNA-binding in gel shift assay similar to wild-type Runx1. In co...

Research paper thumbnail of LOMA: A fast method to generate efficient tagged-random primers despite amplification bias of random PCR on pathogens

BMC Bioinformatics, 2008

Background: Pathogen detection using DNA microarrays has the potential to become a fast and compr... more Background: Pathogen detection using DNA microarrays has the potential to become a fast and comprehensive diagnostics tool. However, since pathogen detection chips currently utilize random primers rather than specific primers for the RT-PCR step, bias inherent in random PCR amplification becomes a serious problem that causes large inaccuracies in hybridization signals.

Research paper thumbnail of RCP is a human breast cancer–promoting gene with Ras-activating function

Journal of Clinical Investigation, 2009

Aggressive forms of cancer are often defined by recurrent chromosomal alterations, yet in most ca... more Aggressive forms of cancer are often defined by recurrent chromosomal alterations, yet in most cases, the causal or contributing genetic components remain poorly understood. Here, we utilized microarray informatics to identify candidate oncogenes potentially contributing to aggressive breast cancer behavior. We identified the Rab-coupling protein RCP (also known as RAB11FIP1), which is located at a chromosomal region frequently amplified in breast cancer (8p11-12) as a potential candidate. Overexpression of RCP in

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