Alexander Zaika, Ph.D.
Assistant Professor of Cancer Biology and Surgery
Vanderbilt University Medical Center
1255 Light Hall
Nashville , TN 37232-2733
Molecular Mechanisms of Tumorigenesis, p53 protein family
p53 protein family, which consists of p53, p63 and p73, plays a pivotal role in regulation of multiple cellular mechanisms including apoptosis, cell cycle control and DNA damage repair. We are interested in understanding the molecular and cellular machinery that underlie the functions of these proteins. Although the role of p53 in human studies is relatively well studied, less is known about p73 and p63. Our analyses demonstrated that p73 and p63 family interact with each-other and these interactions play a critical role in human tumorigenesis. Our data also suggest that these proteins are strongly involved in a response to anticancer curative treatment. We are using a number of different in vitro and in vivo techniques to examine the role of the p53 protein family in cancer development and progression.
- Vilgelm, A, Wei, JX, Piazuelo, MB, Washington, MK, Prassolov, V, El-Rifai, W, Zaika, A DeltaNp73alpha regulates MDR1 expression by inhibiting p53 function. Oncogene, 27(15), 2170-6, 2008.
- Wei, J, O''Brien, D, Vilgelm, A, Piazuelo, MB, Correa, P, Washington, MK, El-Rifai, W, Peek, RM, Zaika, A Interaction of Helicobacter pylori with gastric epithelial cells is mediated by the p53 protein family. Gastroenterology, 134(5), 1412-23, 2008.
- Tomkova, K, El-Rifai, W, Vilgelm, A, Kelly, MC, Wang, TC, Zaika, AI The gastrin gene promoter is regulated by p73 isoforms in tumor cells. Oncogene, 2006.
- Zaika, AI, El-Rifai, W The role of p53 protein family in gastrointestinal malignancies. Cell Death Differ, 13(6), 935-40, 2006.
- Belkhiri, A, Zaika, A, Pidkovka, N, Knuutila, S, Moskaluk, C, El-Rifai, W Darpp-32: a novel antiapoptotic gene in upper gastrointestinal carcinomas. Cancer Res, 65(15), 6583-92, 2005.
- Koon, N, Zaika, A, Moskaluk, CA, Frierson, HF, Knuutila, S, Powell, SM, El-Rifai, W Clustering of molecular alterations in gastroesophageal carcinomas. Neoplasia, 6(2), 143-9, 2004.
- Varis, A, Zaika, A, Puolakkainen, P, Nagy, B, Madrigal, I, Kokkola, A, VÃ¤yrynen, A, KÃ¤rkkÃ¤inen, P, Moskaluk, C, El-Rifai, W, Knuutila, S Coamplified and overexpressed genes at ERBB2 locus in gastric cancer. Int J Cancer, 109(4), 548-53, 2004.
- Slade, N, Zaika, AI, Erster, S, Moll, UM DeltaNp73 stabilises TAp73 proteins but compromises their function due to inhibitory hetero-oligomer formation. Cell Death Differ, 11(3), 357-60, 2004.
- Tomkova, K, Belkhiri, A, El-Rifai, W, Zaika, AI p73 isoforms can induce T-cell factor-dependent transcription in gastrointestinal cells. Cancer Res, 64(18), 6390-3, 2004.
- Joseph, TW, Zaika, A, Moll, UM Nuclear and cytoplasmic degradation of endogenous p53 and HDM2 occurs during down-regulation of the p53 response after multiple types of DNA damage. FASEB J, 17(12), 1622-30, 2003.
- Petrenko, O, Zaika, A, Moll, UM deltaNp73 facilitates cell immortalization and cooperates with oncogenic Ras in cellular transformation in vivo. Mol Cell Biol, 23(16), 5540-55, 2003.
- Mihara, M, Erster, S, Zaika, A, Petrenko, O, Chittenden, T, Pancoska, P, Moll, UM p53 has a direct apoptogenic role at the mitochondria. Mol Cell, 11(3), 577-90, 2003.
- Zaika, AI, Slade, N, Erster, SH, Sansome, C, Joseph, TW, Pearl, M, Chalas, E, Moll, UM DeltaNp73, a dominant-negative inhibitor of wild-type p53 and TAp73, is up-regulated in human tumors. J Exp Med, 196(6), 765-80, 2002.
- Shirangi, TR, Zaika, A, Moll, UM Nuclear degradation of p53 occurs during down-regulation of the p53 response after DNA damage. FASEB J, 16(3), 420-2, 2002.
- Sansome, C, Zaika, A, Marchenko, ND, Moll, UM Hypoxia death stimulus induces translocation of p53 protein to mitochondria. Detection by immunofluorescence on whole cells. FEBS Lett, 488(3), 110-5, 2001.
- Moll, UM, Zaika, A Nuclear and mitochondrial apoptotic pathways of p53. FEBS Lett, 493(2-3), 65-9, 2001.
- Zaika, A, Irwin, M, Sansome, C, Moll, UM Oncogenes induce and activate endogenous p73 protein. J Biol Chem, 276(14), 11310-6, 2001.
- Moll, UM, Erster, S, Zaika, A p53, p63 and p73--solos, alliances and feuds among family members. Biochim Biophys Acta, 1552(2), 47-59, 2001.
- Marchenko, ND, Zaika, A, Moll, UM Death signal-induced localization of p53 protein to mitochondria. A potential role in apoptotic signaling. J Biol Chem, 275(21), 16202-12, 2000.
- Moll, UM, Zaika, A Disrupting the p53-mdm2 interaction as a potential therapeutic modality. Drug Resist Updat, 3(4), 217-221, 2000.
- Kovalev, S, Mateen, A, Zaika, AI, O''Hea, BJ, Moll, UM Lack of defective expression of the ATM gene in sporadic breast cancer tissues and cell lines. Int J Oncol, 16(4), 825-31, 2000.
- Zaika, A, Mozzherin, DJ, Tan, CK, Downey, KM, Fisher, PA A two-dimensional support for selective binding of polyhistidine-tagged proteins: identification of a proliferating cell nuclear antigen point mutant with altered function in vitro. Anal Biochem, 268(2), 193-200, 1999.
- Zaika, A, Marchenko, N, Moll, UM Cytoplasmically "sequestered" wild type p53 protein is resistant to Mdm2-mediated degradation. J Biol Chem, 274(39), 27474-80, 1999.
- Zaika, AI, Kovalev, S, Marchenko, ND, Moll, UM Overexpression of the wild type p73 gene in breast cancer tissues and cell lines. Cancer Res, 59(13), 3257-63, 1999.