@article {159,
	title = {HIPK2 represses beta-catenin-mediated transcription, epidermal stem cell expansion, and skin tumorigenesis.},
	journal = {Proc Natl Acad Sci U S A},
	volume = {104},
	year = {2007},
	month = {2007 Aug 7},
	pages = {13040-5},
	abstract = {<p>Transcriptional control by beta-catenin and lymphoid enhancer-binding factor 1 (LEF1)/T cell factor regulates proliferation in stem cells and tumorigenesis. Here we provide evidence that transcriptional co repressor homeodomain interacting protein kinase 2 (HIPK2) controls the number of stem and progenitor cells in the skin and the susceptibility to develop squamous cell carcinoma. Loss of HIPK2 leads to increased proliferative potential, more rapid G1-S transition in cell cycle, and expansion of the epidermal stem cell compartment. Among the critical regulators of G1-S transition in the cell cycle, only cyclin D1 is selectively up-regulated in cells lacking HIPK2. Conversely, overexpression of HIPK2 suppresses LEF1/beta-catenin-mediated transcriptional activation of cyclin D1 expression. However, deletion of the C-terminal YH domain of HIPK2 completely abolishes its ability to recruit another transcriptional corepressor CtBP and suppress LEF1/beta-catenin-mediated transcription. To determine whether loss of HIPK2 leads to increased susceptibility to tumorigenesis, we treat wild-type, Hipk2+/-, andHipk2-/- mice with the two-stage carcinogenesis protocol. Our results indicate that more skin tumors are induced in Hipk2+/- and Hipk2-/- mutants, with most of the tumors showing shortened incubation time and malignant progression. Together, our results indicate that HIPK2 is a tumor suppressor that controls proliferation by antagonizing LEF1/beta-catenin-mediated transcription. Loss of HIPK2 synergizes with activation of H-ras to induce tumorigenesis.</p>},
	keywords = {Animals, beta Catenin, Carrier Proteins, Cell Proliferation, Cells, Cultured, Cyclin D1, Epidermis, Keratinocytes, Lymphoid Enhancer-Binding Factor 1, Mice, Protein-Serine-Threonine Kinases, Repressor Proteins, Skin Neoplasms, Stem Cells, Transcriptional Activation},
	issn = {0027-8424},
	doi = {10.1073/pnas.0703213104},
	author = {Wei, Guangwei and Ku, Stephen and Ma, Gene K and Saito, Shin{\textquoteright}ichi and Tang, Amy A and Zhang, Jiasheng and Jiang-Hua Mao and Appella, Ettore and Balmain, Allan and Huang, Eric J}
}
