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p205, A potential tumor suppressor, inhibits cell proliferation via multiple pathways of cell cycle regulation
Author(s) -
Asefa Benyam,
Dermott Jonathan M.,
Kaldis Philipp,
Stefanisko Karen,
Garfinkel David J.,
Keller Jonathan R.
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.01.032
Subject(s) - cell cycle , microbiology and biotechnology , cell growth , cell cycle checkpoint , biology , cell , transcription factor , chemistry , biochemistry , gene
p205 is a member of the interferon‐inducible p200 family of proteins that regulate cell proliferation. Over‐expression of p205 inhibits cell growth, although its mechanism of action is currently unknown. Therefore, we evaluated the effect of p205 on the p53 and Rb‐dependent pathways of cell cycle regulation. p205 expression results in elevated levels of p21, and activates the p21 promoter in vitro in a p53‐dependent manner. In addition, p205 induces increased expression of Rb, and binds directly to Rb and p53. Interestingly, p205 also induces growth inhibition independent of p53 and Rb by delaying G2/M progression in proliferating cells, and is a substrate for Cdk2 kinase activity. Finally, we have identified other binding partners of p205 by a yeast two‐hybrid screen, including the paired homeodomain protein HoxB2. Taken together, our results indicate that p205 induces growth arrest by interaction with multiple transcription factors that regulate the cell cycle, including but not entirely dependent on the Rb‐ and p53‐mediated pathways of growth inhibition.