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Regulation
of gene expression by zinc and other small molecules; gene
expression analysis in cancer and other disease states
Regulation
of gene transcription is responsible in large part for the
growth, differentiation, and transformation of eukaryotic cells.
Initiation of RNA synthesis by RNA polymerases is dependent upon
and regulated by transcription factors, a family of DNA binding
proteins whose members interact specifically with promoters,
enhancers and upstream activating sequences of genes. Our
research efforts are directed toward understanding the molecular
biology of eukaryotic transcription factors, endeavors we
believe necessary for ultimately understanding cell growth,
differentiation and transformation. Research activities are
being conducted in four areas: 1) elucidating transcription
factor structure and function utilizing biochemical and in
vitro mutagenesis approaches, 2) cloning and sequencing of
transcription factor genes and cDNAs in order to identify
conserved and functionally important regions in the DNA and
protein sequence, 3) characterizing tissue-specific
transcription factors that may play a role in differentiation
and oncogenesis, and 4) elucidating mechanisms regulating
transcription factor gene expression. Present studies are
focused on families of eukaryotic transcription factors whose
DNA binding domains contain "zinc fingers",
cysteine-rich amino acid motifs known to coordinate zinc ions.
Recent
Publications:
Hanas JS, Hocker JR, Cheng YG, Lerner MR, Brackett DJ,
Lightfoot SA, Hanas RJ, Madhusudhan KT, and Moreland RJ, 2002:
cDNA cloning, DNA binding, and evolution of mammalian
transcription factor IIIA. Gene 282:43-52.
Rodgers JS, Hocker JR, Hanas RJ, Nwosu EC, Hanas JS.
2001: Mercuric ion inhibition of eukaryotic transcription factor
binding to DNA. Biochem Pharmacol.: 61(12):1543-50.
Moreland
RJ, Dresser ME, Rodgers JS, Roe BA, Conaway JW, Conaway RC, Hanas
JS. 2000: Identification of a transcription factor
IIIA-interacting protein. Nucleic Acids Res.:
28(9):1986-93.
Jett
EA, Lerner MR, Lightfoot SA, Hanas JS, Brackett DJ,
Hollingsworth AB. 1999: Prevention of rat mammary carcinoma
utilizing leuprolide as an equivalent to oophorectomy. Breast
Cancer Res Treat.: 58(2):131-6.
Hanas
JS, Rodgers JS, Bantle JA, Cheng YG. 1999: Lead inhibition
of DNA-binding mechanism of Cys(2)His(2) zinc finger proteins. Mol
Pharmacol.: 56(5):982-8.
Hanas
JS, Lerner MR, Lightfoot SA, Raczkowski C, Kastens DJ,
Brackett DJ, Postier RG. 1999: Expression of the
cyclin-dependent kinase inhibitor p21(WAF1/CIP1) and p53 tumor
suppressor in dysplastic progression and adenocarcinoma in
Barrett esophagus. Cancer.: 86(5):756-63.
Hollingsworth,
A.B., Lerner, M.R., Lightfoot, S.A., Wilkerson, K.B., Hanas,
J.S., McCay, P.B., and Brackett, D.J., 1998: Prevention of
DMBA-Induced Mammary Carcinomas Comparing Leuprolide,
Oophorectomy, and Tamoxifen. Breast Cancer Research
47:63-70.
Hanas,
J.S., Koelsch, G., Moreland, R.M., and Wickham, J.Q., 1998:
Differential Requirements of Basic Amino Acids in Transcription
Factor IIIA-5S Gene Interaction. Biochimica et Biophysica
Acta 1398:256-264.
Moreland,
R.J., Hanas, J.S., Conaway, J.W., and Conaway, R.C.,
1998: Mechanism of Action of RNA Polymerase II Elongation Factor
Elongin. J. Biol. Chem. 273:26610-26617.
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