p130, p107, and pRb Are Differentially Regulated in Proliferating Cells and during Cell Cycle Arrest by α-Interferon

• Published in: The Journal of biological chemistry 1998-09, Vol.273 (37), p.23659-23667
• Main Authors: Thomas, Nicholas S.B., Pizzey, Arnold R., Tiwari, Sanjay, Williams, Catherine D., Yang, Jiewu
• Format: Article
• Language: English
• Subjects: B-Lymphocytes - cytology; B-Lymphocytes - drug effects; B-Lymphocytes - metabolism; Base Sequence; Binding Sites; Carrier Proteins; Cell Cycle - drug effects; Cell Cycle - physiology; Cell Cycle Proteins; Cell Division; Cells, Cultured; DNA-Binding Proteins - metabolism; E2F Transcription Factors; E2F1 Transcription Factor; E2F4 Transcription Factor; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - metabolism; Humans; Interferon-alpha - pharmacology; Interferon-alpha - physiology; Nuclear Proteins - metabolism; Oligodeoxyribonucleotides - chemistry; Oligodeoxyribonucleotides - metabolism; Phosphoproteins - metabolism; Phosphorylation; Proteins; Retinoblastoma Protein - metabolism; Retinoblastoma-Binding Protein 1; Retinoblastoma-Like Protein p107; Retinoblastoma-Like Protein p130; T-Lymphocytes - cytology; T-Lymphocytes - drug effects; T-Lymphocytes - metabolism; Transcription Factor DP1; Transcription Factors - metabolism; Tretinoin - pharmacology; Tumor Cells, Cultured
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.273.37.23659

We have determined how the phosphorylation of the retinoblastoma family (pRb, p107, and p130) is governed in individual cell cycle phases of Daudi B-cells during cell cycle exit triggered by α-interferon (α-IFN). α-IFN causes dephosphorylation of pRb and loss of p130 phosphorylated Form 3. However, the change in p130 phosphorylation in response to α-IFN occurs before dephosphorylation of pRb is complete because loss of p130 Form 3 occurs throughout the cell cycle prior to complete arrest in G1, whereas pRb is dephosphorylated only in G1. In contrast, p107 is dephosphorylated and is then depleted from cells as they exit the cell cycle. p130, predominantly in Form 1, and hypophosphorylated pRb bind an E2F DNA binding site; p130 complexes E2F-4, whereas pRb binds both E2F-4 and E2F-1. The phosphorylated forms of E2F-4 that bind to the E2F DNA site are different from hyperphosphorylated E2F-4, which predominates in primary hemopoietic cells in G0. We conclude that although cell cycle arrest induced by α-IFN may be mediated in part by formation of a complex containing p130 and E2F-4, α-IFN does not induce hyperphosphorylation of E2F-4, which characterizes primary hemopoietic cells in G0.