Modulation of E2F Complexes during G0 to S Phase Transition in Human Primary B-lymphocytes

Sman, Jeroen van der; Thomas, N. Shaun B.; Lam, Eric

doi:10.1074/jbc.274.17.12009

Cited by 23 publications

(20 citation statements)

References 55 publications

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“…E2F-4 also bound to the same site (Fig. 3D, lane 1; n=4) and, as we have reported previously (Thomas et al 1998, Van der Sman et al 1999, the more highly phosphorylated forms of E2F-4 bound preferentially (compare with lanes 3 and 4). However, we did not detect E2F-1 bound to the E2F WT DNA site (not shown).…”

Section: Activity Of the Prb Familysupporting

confidence: 63%

“…GLC do contain E2F-4 ( Fig. 2A, lanes 4, 5; n=15), and the phosphorylated forms of E2F-4 present co-migrate with those in proliferating cells (lane 6) rather than the hyperphosphorylated form (lane 3) which we have shown is present in quiescent primary haemopoietic cells such as T-or B-lymphocytes or CD34+ cells (Williams et al 1997a, Thomas et al 1998, Van der Sman et al 1999. We also detected the hypophosphorylated form of p107 in the GLC samples ( Fig.…”

Section: Expression Of Proteins That Regulate Cell Proliferationmentioning

confidence: 99%

“…Pull-down assays were carried out as described previously (Thomas et al 1998, Van der Sman et al 1999) with 5 10 5 -2·5 10 6 GLC or with 1-5 10 6 proliferating or quiescent T-lymphocytes which were lysed in 800 µl low salt buffer. Solutions were kept on ice and all manipulations were carried out in a 5 C cold-room.…”

Section: E2f Dna-binding Site Pull-down Assays and Western Blottingmentioning

confidence: 99%

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p107 is active in the nucleolus in non-dividing human granulosa lutein cells

Green¹,

Chatterjee²,

Mcgarrigle³

et al. 2000

Journal of Molecular Endocrinology

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Cells are maintained in a quiescent state by members of the retinoblastoma protein family, pRb and p130. Both are phosphoproteins and hypophosphorylated forms of pRb and p130 bind and repress the activity of E2F transcription factors, thereby preventing entry into the cell cycle. Mitogenic stimulation causes activation of cyclin dependent kinases (cdk) that phosphorylate both pRb and p130, thereby releasing E2F factors which stimulate the transcription of a number of genes that are required for DNA synthesis and for regulating the cell cycle. In non-dividing cells, cdks are maintained in an inactive state by cdk inhibitor proteins such as p27 Kip1 . The aim of our study was to determine how E2F complexes are regulated during the differentiation of human primary granulosa lutein cells (GLC) of the corpus luteum (CL). The CL is formed in the ovary after ovulation at the terminal stage of folliculogenesis after completion of maturation and differentiation of Graafian follicles. As shown by flow cytometry GLC are not dividing, being predominantly in the G 0 /G 1 phase of the cell cycle and, consistent with this, they contain the cdk inhibitor protein, p27Kip1 , but not E2F-1 which is normally expressed only in proliferating cells. The GLC do express E2F-4, hypophosphorylated pRb, p130 forms 1 and 2 and, surprisingly, hypophosphorylated p107. p107 is normally present only in dividing cells where it regulates E2F activity during the cell cycle. These forms of pRb, p130 as well as p107, together with E2F-4 are all active in that they can bind an E2F DNA-binding site in a pull-down assay. Immunocytochemistry shows that these proteins are expressed in almost all GLC but have different sub-cellular distribution: p107 is concentrated in nucleoli, while p130 and E2F-4 show relatively even nuclear and cytoplasmic distributions. Both pRb and p130 have been implicated previously in repressing E2F activity in many different cell types during cell cycle arrest in G 0 /G 1 . We conclude that p107 is active in human primary GLC but its nucleolar localisation would suggest that it represses ribosomal RNA synthesis rather than E2F activity.

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Section: Activity Of the Prb Familysupporting

confidence: 63%

Section: Expression Of Proteins That Regulate Cell Proliferationmentioning

confidence: 99%

Section: E2f Dna-binding Site Pull-down Assays and Western Blottingmentioning

confidence: 99%

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p107 is active in the nucleolus in non-dividing human granulosa lutein cells

Green¹,

Chatterjee²,

Mcgarrigle³

et al. 2000

Journal of Molecular Endocrinology

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show abstract

“…Moreover, terminal differentiation, evidenced by Ig secretion observed on days 7 and 8, was associated with a significant decrease in the total pRb level, which was not compensated by an increase in the amounts of other members of the pRb family such as p130 or p107. This absence or lower pRb expression was also observed in resting B cells that had not yet entered the cell cycle and is probably a property of B lymphocytes that are not cycling (45). Ig secretion also takes place during the G 1 phase in cycling B cell lines, because Ig secretion by Ramos cells was significantly increased when they were arrested by FCS deprivation in early G 1 .…”

Section: Discussionmentioning

confidence: 84%

The Expression of p18INK4 and p27kip1 Cyclin-Dependent Kinase Inhibitors Is Regulated Differently During Human B Cell Differentiation

Schrantz

Beney

Auffredou

et al. 2000

The Journal of Immunology

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Cell cycle progression is under the control of cyclin-dependent kinases (cdks), the activity of which is dependent on the expression of specific cdk inhibitors. In this paper we report that the two cdk inhibitors, p27Kip1 and p18INK4c, are differently expressed and control different steps of human B lymphocyte activation. Resting B cells contain large amounts of p27Kip1 and no p18INK4c. In vitro stimulation by Staphylococcus aureus Cowan 1 strain or CD40 ligand associated with IL-10 and IL-2 induces a rapid decrease in p27Kip1 expression combined with cell cycle entry and progression. In contrast, in vitro Ig production correlates with specific expression of p18INK4c and early G1 arrest. This G1 arrest is associated with inhibition of cyclin D3/cdk6-mediated retinoblastoma protein phosphorylation by p18INK4c. A similar contrasting pattern of p18INK4c and p27Kip1 expression is observed both in B cells activated in vivo and in various leukemic cells. Expression of p18INK4c was also detected in various Ig-secreting cell lines in which both maximum Ig secretion and specific p18INK4c expression were observed during the G1 phase. Our study shows that p27Kip1 and p18INK4c have different roles in B cell activation; p27Kip1 is involved in the control of cell cycle entry, and p18INK4c is involved in the subsequent early G1 arrest necessary for terminal B lymphocyte differentiation.

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“…The DNA probe was a double stranded oligonucleotide (5Ј-CTAGATCTAGTTT-TCGCGCTTAAATTTGA-3Ј) containing the distal E2F binding site from the adenovirus type 5 E2a promoter (34). Each E2F binding reaction contained 7 g of nuclear extract, 10 l of DNA binding reaction mix (20 mM HEPES, pH 7.9, 40 mM KCl, 6 mM MgCl 2 , 1 mM EGTA, 1 mM dithiothreitol, 0.1% Nonidet P-40, 10% glycerol, 15 g of bovine serum albumin, 1 g of sonicated herring sperm DNA) and 5 ng of 32 P-labeled DNA probe.…”

Section: Methodsmentioning

confidence: 99%

Accelerated G1 Phase Progression Induced by the Human T Cell Leukemia Virus Type I (HTLV-I) Tax Oncoprotein

Lemoine

Marriott

2001

Journal of Biological Chemistry

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Tax, the human T cell leukemia virus type I oncoprotein, plays a crucial role in viral transformation and the development of the virally associated disease adult T cell leukemia. Because oncogenesis involves alterations in cell growth, it is important to examine the effects of Tax on cell cycle progression. Using a synchronized cell system, we have found that Tax expression accelerates G 1 phase progression and S phase entry with concomitant DNA replication. This accelerated progression is accompanied by an earlier onset of cdk2 kinase activity. In contrast to the shortening of G 1 phase, the length of S phase is unaffected by Tax expression. As a result of a more rapid cell cycle progression, cells expressing Tax exhibit faster growth kinetics and display an altered cell cycle distribution. Additionally, the decreased time allowed for growth in the presence of Tax results in a decreased cell size. Tax-associated acceleration of cell cycle progression may play a role in the ability of this viral oncoprotein to mediate cellular transformation and promote the development of human T cell leukemia virus type I-associated diseases.

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Modulation of E2F Complexes during G0 to S Phase Transition in Human Primary B-lymphocytes

Cited by 23 publications

References 55 publications

p107 is active in the nucleolus in non-dividing human granulosa lutein cells

p107 is active in the nucleolus in non-dividing human granulosa lutein cells

The Expression of p18INK4 and p27kip1 Cyclin-Dependent Kinase Inhibitors Is Regulated Differently During Human B Cell Differentiation

Accelerated G1 Phase Progression Induced by the Human T Cell Leukemia Virus Type I (HTLV-I) Tax Oncoprotein

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