The PI has cloned and characterized a novel p53 homolgoue p40 (AIS), one of several variants (p40/51/63/73L) that is encoded by the 3q27-28 gene locus. Although the AIS protein can interact with p53 binding sites and transcriptionally activate downstream targets of p53, the Pi has found no evidence of a tumor suppressor function of AIS. On the contrary, accumulating evidence supports and oncogenic role for this gene. The PI has sown that: (i) the AIS gene is amplified in primary lung cancer and head and neck and cancer squamous cell carcinoma (SCC) cell lines by FISH analysis; (ii) chromosomal amplification of AIS is associated with increased AIS RNA expression and AIS protein accumulation; (iii) the AIS gene product is able to transform Rat1a cells in culture and leads to increased tumor growth in nude mice; (iv) AIS interacts with p53 in vitro and in vivo, and suppressed p53-mediated transactivation activity on target genes. The PI now proposes to examine in depth the role of AIS in human cancer. The PI will study AIS activation in the progression of SCC of the HN and lung and other human tumors. Since AIS is a putative transcription factor the PI will identify the downstream targets of AIS by novel assays. The PI will seek to identify the transcriptional binding site of AIS using yeast genetic strategies in order to clarify the target sites involved in cell proliferation, oncogenesis and apoptosis. Finally, based on results from the PI that p53 associates with AIS in vitro and in vivo, the nature of this protein-protein interaction will be characterized. These studies will yield new insights into the oncogenic activity of AIS and will allow further elucidation of its function in human tumorigenesis.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project (R01)
Project #
Application #
Study Section
Pathology B Study Section (PTHB)
Program Officer
Sandberg, Ann
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Johns Hopkins University
Schools of Medicine
United States
Zip Code
Huang, Yiping; Chuang, Alice Y; Ratovitski, Edward A (2011) Phospho-?Np63?/miR-885-3p axis in tumor cell life and cell death upon cisplatin exposure. Cell Cycle 10:3938-47
Sen, Tanusree; Sen, Nilkantha; Huang, Yiping et al. (2011) Tumor protein p63/nuclear factor ?B feedback loop in regulation of cell death. J Biol Chem 286:43204-13
Sen, Tanusree; Sen, Nilkantha; Brait, Mariana et al. (2011) DeltaNp63alpha confers tumor cell resistance to cisplatin through the AKT1 transcriptional regulation. Cancer Res 71:1167-76
Huang, Y; Chuang, A; Hao, H et al. (2011) Phospho-?Np63? is a key regulator of the cisplatin-induced microRNAome in cancer cells. Cell Death Differ 18:1220-30
Ratovitski, Edward A (2011) ?Np63?/IRF6 interplay activates NOS2 transcription and induces autophagy upon tobacco exposure. Arch Biochem Biophys 506:208-15
Chatterjee, Aditi; Chang, Xiaofei; Sen, Tanusree et al. (2010) Regulation of p53 family member isoform DeltaNp63alpha by the nuclear factor-kappaB targeting kinase IkappaB kinase beta. Cancer Res 70:1419-29
Huang, Yiping; Ratovitski, Edward A (2010) Phosphorylated TP63 induces transcription of RPN13, leading to NOS2 protein degradation. J Biol Chem 285:41422-31
Chatterjee, Aditi; Sen, Tanusree; Chang, Xiaofei et al. (2010) Yes-associated protein 1 regulates the stability of DeltaNp63alpha. Cell Cycle 9:162-7
Huang, Yiping; Chuang, Alice Y; Romano, Rose-Anne et al. (2010) Phospho-DeltaNp63alpha/NF-Y protein complex transcriptionally regulates DDIT3 expression in squamous cell carcinoma cells upon cisplatin exposure. Cell Cycle 9:328-38
Sen, Tanusree; Chang, Xiaofei; Sidransky, David et al. (2010) Regulation of ýýNp63ýý by NFýýýý. Cell Cycle 9:4841-7

Showing the most recent 10 out of 28 publications