Sp1 as G1 cell cycle phase specific transcription factor in epithelial cells.
Sp1 binding sites have been identified in enhancer/promoter regions of several growth and cell cycle regulated genes, and it has been shown that Sp1 is increasingly phosphorylated in G1 phase of the cell cycle. Interactions of Sp1 with proteins involved in control of cell cycle and tumor formation have been reported. Here we show that expression of Sp1 protein predominates in the G1 phase of the cell cycle in epithelial cells. This is achieved by proteasome-dependent degradation. Inhibition of endogeneous Sp1 activity by a dominant-negative Sp1 mutant was associated with a cell cycle arrest in G1 phase, a strongly reduced expression of cyclin D1, the EGF-receptor and increased levels of p27Kip1. We have thus identified Sp1 as an important regulator of the cell cycle in G1 phase.
Grinstein
Edgar
E
Institut für Transplantationsdiagnostik und Zelltherapeutika, Heinrich Heine Universität Düsseldorf, Moorenstrasse 5, 40225 Düsseldorf, Germany. Edgar.Grinstein@itz.uni-duesseldorf.de
Jundt
Franziska
F
Weinert
Inge
I
Wernet
Peter
P
Royer
Hans-Dieter
HD
D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D002999:Clone Cells; D019938:Cyclin D1 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27; D003546:Cysteine Endopeptidases / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D016193:G1 Phase; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D007700:Kinetics; D009097:Multienzyme Complexes / Q000378:metabolism; D009154:Mutation; D046988:Proteasome Endopeptidase Complex; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D018797:Cell Cycle Proteins; D009097:Multienzyme Complexes; D016329:Sp1 Transcription Factor; D025521:Tumor Suppressor Proteins; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; D066246:ErbB Receptors; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex