Background
Previous Appointments:
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Research Associate, Department of Biochemistry,
Hong Kong University of Science and Technology
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Postdoctoral fellow,
Institute of Molecular Biology, The University of Hong Kong
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Research Assistant Professor, Department of Pathology and
Biochemistry, The
University of Hong Kong
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Research
Research Interests:
Current Projects:
Neuronal Cdc2-like kinase (Nclk)
Neuronal cdc2-like kinase (Nclk) has been shown to play an
important role in neuronal differentiation, neuro-cytoskeleton
dynamics, and neurite extension. Aberrant of Nclk activity has
been implicated in a number of neurodegenerative diseases
including Alzheimer’s disease and Parkinson’s disease. Nclk
consists of a catalytic subunit, called cyclin dependent
protein kinase 5 (Cdk5), and a 25 kDa regulatory subunit
derived proteolytically from a 35 kDa neuronal-specific
protein, called neuronal Cdk5 activator. Although Cdk5 protein
exists ubiquitously, Nclk activity can only be found in brain
because of the restricted expression of Cdk5 activator. This
suggests that the activator is the crucial modulator for the
Nclk activity. Thus our current researches focus on the
identification of proteins that can interact with Cdk5
activators and can modulate the Cdk5 activity.
p21-activated protein kinase (Pak)
The small Rho GTPases family (including RhoA, Cdc42 and Rac1),
which belongs to Ras small GTPase superfamily, is involved in
a number of cellular processes including gene regulation, cell
migration and cell division. Emerging evidences has
shown that Rho GTPases also play a vital role in the
regulation of neurite outgrowth and cell migration. One
of the downstream effectors of Cdc42 and Rac1 is called
p21-activated protein kinase (Pak), which contains a highly
conserved N-terminal Cdc42/Rac1 binding domain and a
C-terminal kinase domain. Six members of Pak kinase
family have been identified and they are subdivided into 2
groups. Pak5, which belongs to the group II Pak family,
is found to be highly expressed in brain and stimulates
neurite outgrowth by downregulation of RhoA. Using the
yeast-2 hybrid screening, we have identified several potential
cellular partners of Pak5 and would like to further
characterize the functional outcome of their interaction.
Recently, we also found that group I Pak family member, Pak1,
is overexpressed in liver cancer, which is one of the most
common cancers worldwide and in Hong Kong. Thus, our
researches also focus on the molecular mechanism by which Pak
1 induces hepatocarcinogenesis.
Centrosome and cancer
Emerging evidence suggests that supernumerary centrosomes
drive chromosomal instability and is linked to oncogenesis.
Several viral oncoproteins, such as human papillomavirus (HPV)
type 16 E6 and E7 and hepatitis B virus X protein (HBx), have
been shown to transform cells by promoting centrosome
abnormalities and formation of multipolar spindles. Thus it
appears that induction of centrosome amplification may be a
common strategy for viral-mediated oncogenesis. We have
recently characterised a novel cellular centrosomal protein,
which we named TAX1BP2 and have shown to play an important
role in centrosome duplication. Thus we would like to
understand further the molecular signaling of TAX1BP2 and how
centrosome overduplication contributes to the development of
cancer.
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Selected Publications
(full list of publication:
publication list)
*Corresponding author
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Ching, Y.P*.
Qi, Z., Wang, H.C. (2000). Cloning of Three
Novel Neuronal Cdk5 Activator Binding Protein.
Gene, 242, 285-294.
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Ching, Y.P.,
Pang, A.S., Lam, W.H., Qi, R.Z., Wang, J.H.
(2002).
Identification of a neuronal Cdk5 activator-binding
protein as Cdk5 inhibitor. J.
Biol. Chem., 277(18), 15237-15240.
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Ching, Y.P.*,
Leong, V.Y., Wong, C.M., Kung, H.F. (2003).
Identification of an autoinhibitory domain of
p21-activated protein kinase 5. J. Biol.
Chem.,
278 (36): 33621-4.
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Ching, Y.P.,
Wong, C.M., Chan, S.F., Leung, T.H., Ng, D.C., Jin, D.Y.,
Ng, I.O.
(2003).
Deleted in Liver Cancer (DLC) 2 Encodes a RhoGAP Protein
with Growth Suppressor Function and Is Underexpressed in
Hepatocellular Carcinoma. J. Biol.
Chem., 278(12): 10824-30.
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Leung, T.H.Y., Ching, Y.P., Yam, J.W.P., Wong, C.M.,
Yau, T.O., Jin, D.Y. and Ng, I.O.L.
(2005).
Deleted in liver cancer 2, DLC2, suppresses cell
transformation via inhibition of RhoA activity.
PNAS,
102:15207-12.
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Ching, Y.P.,
Chan S.F., Jeang, K.T. and Jin, D.Y.
(2006).
Retroviral oncoprotein Tax targets coiled-coil centrosomal
protein TAX1BP2 to induce centrosome overduplication.
Nature Cell Biology, 8:717-724.
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Ching, Y.P.*,
Leong, V.Y.L., Lee, M.F., Xu, H., Jin, D.Y. and Ng, I.O.L.
(2007).
Pak1 is overexpressed in hepatocellular carcinoma and
enhances cancer metastasis involving JNK activation and
paxillin phosphorylation. Cancer Res.,
67:3601-3608.
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Ma, C., Ying, C., Yuan, Z., Song, B., Li, D., Liu, Y.,
Lai, B., Li, W., Chen, R., Ching, Y.P., Li, M.
Dp5 is a c-Jun target gene and required for apoptosis
induced by potassium deprivation in cerebellar granule
neurons.
J. Biol. Chem., in press.
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Collaborations
Prof. Grahame Hardie, Professor of Cellular Signaling,
University of Dundee, UK
Dr. Dong-Yan Jin, Department of Biochemistry, The University
of Hong Kong, HK
Prof. Irene Oi-Lin Ng, Department of Pathology, The University
of Hong Kong, HK
Prof. Mingtao Li, Zhongshan School of Medicine, Sun Yat-sen
University, China
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