Expression and characterization of Syrian golden hamster p16, a homologue of human tumor suppressor p16INK4A

Junan Li; Dongyan Qin; Thomas J. Knobloch; Ming Daw Tsai; Christopher M. Weghorst; W. Scott Melvin; Peter Muscarella

doi:10.1016/S0006-291X(03)00577-1

Expression and characterization of Syrian golden hamster p16, a homologue of human tumor suppressor p16^INK4A

Junan Li, Dongyan Qin, Thomas J. Knobloch, Ming Daw Tsai, Christopher M. Weghorst, W. Scott Melvin, Peter Muscarella

Surgery

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

The p16^INK4A/CDKN2A tumor suppressor gene is known to be inactivated in up to 98% of human pancreatic cancer specimens and represents a potential target for novel therapeutic intervention. Chemically induced pancreatic tumors in Syrian golden hamsters have been demonstrated to share many morphologic and biological similarities with human pancreatic tumors and this model may be appropriate for studying therapies targeting p16^INK4A/CDKN2A. The purpose of this study was to investigate the fundamental biochemistry of hamster P16 protein. Using both in vivo and in vitro approaches, the CDK4 binding affinity, kinase inhibitory activity, and thermodynamic stability of hamster and human P16 proteins were evaluated. Furthermore, a structural model of hamster P16 protein was generated. These studies demonstrate that hamster P16 protein is biochemically indistinguishable from human P16 protein. From a biochemical perspective, these data strongly support the study of p16-related pancreatic oncogenesis and cancer therapies in the hamster model.

Original language	English (US)
Pages (from-to)	241-247
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	304
Issue number	2
DOIs	https://doi.org/10.1016/S0006-291X(03)00577-1
State	Published - May 2 2003

Keywords

Functional characterization
P16
Structural modeling
Syrian golden hamster

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/S0006-291X(03)00577-1

Cite this

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title = "Expression and characterization of Syrian golden hamster p16, a homologue of human tumor suppressor p16INK4A",

abstract = "The p16INK4A/CDKN2A tumor suppressor gene is known to be inactivated in up to 98% of human pancreatic cancer specimens and represents a potential target for novel therapeutic intervention. Chemically induced pancreatic tumors in Syrian golden hamsters have been demonstrated to share many morphologic and biological similarities with human pancreatic tumors and this model may be appropriate for studying therapies targeting p16INK4A/CDKN2A. The purpose of this study was to investigate the fundamental biochemistry of hamster P16 protein. Using both in vivo and in vitro approaches, the CDK4 binding affinity, kinase inhibitory activity, and thermodynamic stability of hamster and human P16 proteins were evaluated. Furthermore, a structural model of hamster P16 protein was generated. These studies demonstrate that hamster P16 protein is biochemically indistinguishable from human P16 protein. From a biochemical perspective, these data strongly support the study of p16-related pancreatic oncogenesis and cancer therapies in the hamster model.",

keywords = "Functional characterization, P16, Structural modeling, Syrian golden hamster",

author = "Junan Li and Dongyan Qin and Knobloch, {Thomas J.} and Tsai, {Ming Daw} and Weghorst, {Christopher M.} and {Scott Melvin}, W. and Peter Muscarella",

note = "Funding Information: The authors gratefully acknowledge Dr. Bruce C. Casto for critical review of the manuscript. This work was supported in part by NCI Grant CA69472 to M.-D.T., NIH/NIDCR (RO1-DE11943), NIH/NCI (P30-CA16058) and the Phi Beta Psi Sorority to C.M.W. ",

year = "2003",

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doi = "10.1016/S0006-291X(03)00577-1",

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T1 - Expression and characterization of Syrian golden hamster p16, a homologue of human tumor suppressor p16INK4A

AU - Li, Junan

AU - Qin, Dongyan

AU - Knobloch, Thomas J.

AU - Tsai, Ming Daw

AU - Weghorst, Christopher M.

AU - Scott Melvin, W.

AU - Muscarella, Peter

N1 - Funding Information: The authors gratefully acknowledge Dr. Bruce C. Casto for critical review of the manuscript. This work was supported in part by NCI Grant CA69472 to M.-D.T., NIH/NIDCR (RO1-DE11943), NIH/NCI (P30-CA16058) and the Phi Beta Psi Sorority to C.M.W.

PY - 2003/5/2

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N2 - The p16INK4A/CDKN2A tumor suppressor gene is known to be inactivated in up to 98% of human pancreatic cancer specimens and represents a potential target for novel therapeutic intervention. Chemically induced pancreatic tumors in Syrian golden hamsters have been demonstrated to share many morphologic and biological similarities with human pancreatic tumors and this model may be appropriate for studying therapies targeting p16INK4A/CDKN2A. The purpose of this study was to investigate the fundamental biochemistry of hamster P16 protein. Using both in vivo and in vitro approaches, the CDK4 binding affinity, kinase inhibitory activity, and thermodynamic stability of hamster and human P16 proteins were evaluated. Furthermore, a structural model of hamster P16 protein was generated. These studies demonstrate that hamster P16 protein is biochemically indistinguishable from human P16 protein. From a biochemical perspective, these data strongly support the study of p16-related pancreatic oncogenesis and cancer therapies in the hamster model.

AB - The p16INK4A/CDKN2A tumor suppressor gene is known to be inactivated in up to 98% of human pancreatic cancer specimens and represents a potential target for novel therapeutic intervention. Chemically induced pancreatic tumors in Syrian golden hamsters have been demonstrated to share many morphologic and biological similarities with human pancreatic tumors and this model may be appropriate for studying therapies targeting p16INK4A/CDKN2A. The purpose of this study was to investigate the fundamental biochemistry of hamster P16 protein. Using both in vivo and in vitro approaches, the CDK4 binding affinity, kinase inhibitory activity, and thermodynamic stability of hamster and human P16 proteins were evaluated. Furthermore, a structural model of hamster P16 protein was generated. These studies demonstrate that hamster P16 protein is biochemically indistinguishable from human P16 protein. From a biochemical perspective, these data strongly support the study of p16-related pancreatic oncogenesis and cancer therapies in the hamster model.

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KW - Structural modeling

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