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

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)241-247
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume304
Issue number2
DOIs
StatePublished - May 2 2003
Externally publishedYes

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Mesocricetus
Cricetinae
Tumors
Neoplasms
Biochemistry
Proteins
Pancreatic Neoplasms
Thermodynamic stability
Phosphotransferases
Genes
Structural Models
Tumor Suppressor Genes
Thermodynamics
Carcinogenesis
Therapeutics
human P16 protein

Keywords

  • Functional characterization
  • P16
  • Structural modeling
  • Syrian golden hamster

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Expression and characterization of Syrian golden hamster p16, a homologue of human tumor suppressor p16INK4A. / Li, Junan; Qin, Dongyan; Knobloch, Thomas J.; Tsai, Ming Daw; Weghorst, Christopher M.; Melvin, W. Scott; Muscarella, Peter.

In: Biochemical and Biophysical Research Communications, Vol. 304, No. 2, 02.05.2003, p. 241-247.

Research output: Contribution to journalArticle

Li, Junan ; Qin, Dongyan ; Knobloch, Thomas J. ; Tsai, Ming Daw ; Weghorst, Christopher M. ; Melvin, W. Scott ; Muscarella, Peter. / Expression and characterization of Syrian golden hamster p16, a homologue of human tumor suppressor p16INK4A. In: Biochemical and Biophysical Research Communications. 2003 ; Vol. 304, No. 2. pp. 241-247.
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