John F. Boylan
Wilmington University
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Publication
Featured researches published by John F. Boylan.
Oncogene | 2003
Alex J. Bowers; Sheila Scully; John F. Boylan
Regions of hypoxia are a hallmark of solid tumors. Tumor cells modulate the regulation of specific genes allowing adaptation and survival in the harsh hypoxic environment. We have identified SKIP3, a novel human kinase-like gene, which is overexpressed in multiple human tumors and is regulated by hypoxia. SKIP3 is an ortholog of the Drosophila tribbles, rat NIPK, dog C5FW, and human C8FW genes. Drosophila tribbles is involved in slowing cell-cycle progression during Drosophila development, but little is known regarding the function or tissue distribution of the vertebrate orthologs. We show that the normal tissue expression of SKIP3 is confined to human liver, while multiple primary human lung, colon, and breast tumors express high levels of SKIP3 transcript. Endogenous SKIP3 protein accumulates within 48 h under hypoxic growth conditions in HT-29 and PC-3 cells, with upregulation of the SKIP3 mRNA transcript by 72 h. We identified activating transcription factor 4 (ATF4) as a SKIP3-binding partner using the yeast-two-hybrid assay. Coexpression of SKIP3 and ATF4 showed that SKIP3 is associated with the proteolysis of ATF4, which can be blocked using a proteosome inhibitor. These results indicate that SKIP3 may be an important participant in tumor cell growth.
Bioorganic & Medicinal Chemistry Letters | 2001
Thais M. Sielecki; Tricia L. Johnson; Jie Liu; Jodi K. Muckelbauer; Robert H. Grafstrom; Sarah Cox; John F. Boylan; Catherine R. Burton; Haiying Chen; Angela Smallwood; Chong-Hwan Chang; Michael Boisclair; Pamela A. Benfield; George L. Trainor; Steven P. Seitz
Quinazolines have been identified as inhibitors of CDK4/D1 and CDK2/E. Aspects of the SAR were investigated using solution-phase, parallel synthesis. An X-ray crystal structure was obtained of quinazoline 51 bound in CDK2 and key interactions within the ATP binding pocket are defined.
Bioorganic & Medicinal Chemistry Letters | 2001
David J. Carini; Robert F. Kaltenbach; Jie Liu; Pamela A. Benfield; John F. Boylan; Michael Boisclair; Leonardo Brizuela; Catherine R. Burton; Sarah Cox; Robert H. Grafstrom; Barbara Ann Harrison; Kimberly Harrison; Emeka Akamike; Jay A. Markwalder; Yuki Nakano; Steven P. Seitz; George L. Trainor; Thais M. Sielecki
A new structural type of kinase inhibitor, containing a benzocarbazole nucleus, has been identified. Members of the series are selective for inhibition of the cyclin dependent kinase family of enzymes. Although the cdks are highly homologous, representatives of the series showed intra-cdk selectivities, especially for cdk4. SAR studies elucidated the important features of the molecules for inhibition.
Archive | 2000
Catherine Adams Burton; John F. Boylan; Candy Robinson; Janet S. Kerr; Pamela A. Benfield
The machinery of the cell cycle provides a mechanism for the duplication of cellular DNA during cell division and the appropriate distribution of this DNA to resulting daughter cells. It is important for cell survival that this process occurs in a highly regulated and controlled manner to ensure the accurate transmission of genetic material. Dividing eukaryotic cells are equipped with surveillance mechanisms to ensure that cell cycle progression does not occur if conditions are inappropriate, for example, if DNA is damaged or nucleotide supplies are limiting. These mechanisms have collectively been referred to as checkpoint control. Failure of checkpoint control leads to inappropriate cell division and the accumulation of DNA damage that is the hallmark of human tumor cells [4, 5].
Journal of Medicinal Chemistry | 2000
Thais M. Sielecki; John F. Boylan; Pamela A. Benfield; George L. Trainor
Gene | 2004
Alex J. Bowers; John F. Boylan
Journal of Medicinal Chemistry | 2002
Eddy W. Yue; C. Anne Higley; Susan V. Dimeo; David John Carini; David A. Nugiel; Carrie Benware; Pamela A. Benfield; Catherine R. Burton; Sarah Cox; Robert H. Grafstrom; Lisa Sisk; John F. Boylan; Jodi K. Muckelbauer; Angela Smallwood; Haiying Chen; Chong-Hwan Chang; Steven P. Seitz; George L. Trainor
Experimental Cell Research | 1999
John F. Boylan; Lynn Leffet; Alex J. Bowers; Weijun Pan
Archive | 2001
John F. Boylan; Alex J. Bowers
Archive | 2006
John F. Boylan; Alex J. Bowers