p205, a potential tumor suppressor, inhibits cell proliferation via multiple pathways of cell cycle regulation.
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.
Asefa
Benyam
B
Laboratory of Molecular Immunoregulation, Center for Cancer Research, National Cancer Institute-Frederick, Building 560, Room 31-56, Frederick, MD 21702-1201, USA.
Dermott
Jonathan M
JM
Kaldis
Philipp
P
Stefanisko
Karen
K
Garfinkel
David J
DJ
Keller
Jonathan R
JR
D000818:Animals; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D016195:G2 Phase; D018398:Homeodomain Proteins / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000502:physiology*; D011485:Protein Binding; D016160:Retinoblastoma Protein / Q000378:metabolism; D014157:Transcription Factors / Q000302:isolation & purification / Q000378:metabolism; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020798:Two-Hybrid System Techniques
C484444:HIN-200 protein, mouse; D018398:Homeodomain Proteins; C490111:Hoxb2 protein, mouse; C509511:Ifi205 protein, mouse; D009687:Nuclear Proteins; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D051357:Cyclin-Dependent Kinase 2