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Role of the Chkl Kinase in Cell Cycle Checkpoint Response in Breast Epithelial Cells

机译:Chk1激酶在乳腺上皮细胞细胞周期检查点反应中的作用

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P63 is a recently identified homolog of P53 that is found in the basal layer of several epitherial tissues such as the epidermis, oral mucosa, prostate, urogenital tract, and mammary gland. Studies with p63-/-mice and analysis of several human autosomal dominant disorders with germline p63 mutations suggest p63 involvement in maintaining epithelial stem cell populations. However, the biochemical mechanisms by which p63 functions are not well understood. The goals of the current study were to determine the splice variants that are expressed in primary human mammary epithelial cells (HMECs) and the biochemical activity p63 has in these epithelial cell populations. Progress to date includes (i) Cloning of p63 splice variants and development of assay systems in primary epidermal cell cultures to analyze p63 expression and biochemical activity; (ii) determining that p63 represses transcription and binds directly to p53 consensus sites in the p2l and l4-3-3o promoters in ritro and in vivo in HEKs and HMECs; (iii) development of optimal growth conditions for primary human mammary epithelial cells; (iv) determining that %Np63Q is the predominant splice variant expressed in HMECs; (v) determining that %Np63a is a phosphoprotein and how phosphorylation affects p63 function. It is critical to obtain a more thorough understanding of how p63 works at the rnolecular level in HMECs to better understand the role of p63 in breast cancer development.

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