E2F-dependent induction of p14ARF during cell cycle re-entry in human T cells.

TY - JOUR

T1 - E2F-dependent induction of p14ARF during cell cycle re-entry in human T cells.

AU - del Arroyo, Ana Gutierrez

AU - El Messaoudi, Selma

AU - Clark, Paula A

AU - James, Marion

AU - Stott, Francesca

AU - Bracken, Adrian

AU - Helin, Kristian

AU - Peters, Gordon

N1 - Keywords: Base Sequence; Cell Cycle; Cell Line; Cells, Cultured; E2F Transcription Factors; Humans; Molecular Sequence Data; T-Lymphocytes; Tumor Suppressor Protein p14ARF

PY - 2007

Y1 - 2007

N2 - The ARF protein, encoded by alternate exon usage within the CDKN2A locus, provides a link between the retinoblastoma (pRb) and p53 tumor suppressor pathways. Agents that disable pRb or otherwise impinge on the E2F family of transcription factors induce expression of ARF, resulting in stabilization of p53 and activation of p53-regulated genes. However, in some cell types ARF is not induced upon cell cycle re-entry, as expected of a conventional E2F target gene, leading to the suggestion that the ARF promoter only responds to supra-physiological or aberrant levels of E2F. These properties have recently been attributed to a variant E2F binding site but attempts to map specific response elements within the ARF promoter have generally yielded confusing answers. Here we show that in IL2-dependent T-lymphocytes, ARF expression is induced as cells progress from G(0) into S phase, in parallel with other bona fide E2F target genes. This is accompanied by increased association of E2F1 with the endogenous ARF promoter. Our findings suggest that the ability of ARF to register normal proliferative cues depends on the levels of E2F generated in different settings and argue against the idea that it reacts exclusively to oncogenic signals. Udgivelsesdato: 2007-Aug

AB - The ARF protein, encoded by alternate exon usage within the CDKN2A locus, provides a link between the retinoblastoma (pRb) and p53 tumor suppressor pathways. Agents that disable pRb or otherwise impinge on the E2F family of transcription factors induce expression of ARF, resulting in stabilization of p53 and activation of p53-regulated genes. However, in some cell types ARF is not induced upon cell cycle re-entry, as expected of a conventional E2F target gene, leading to the suggestion that the ARF promoter only responds to supra-physiological or aberrant levels of E2F. These properties have recently been attributed to a variant E2F binding site but attempts to map specific response elements within the ARF promoter have generally yielded confusing answers. Here we show that in IL2-dependent T-lymphocytes, ARF expression is induced as cells progress from G(0) into S phase, in parallel with other bona fide E2F target genes. This is accompanied by increased association of E2F1 with the endogenous ARF promoter. Our findings suggest that the ability of ARF to register normal proliferative cues depends on the levels of E2F generated in different settings and argue against the idea that it reacts exclusively to oncogenic signals. Udgivelsesdato: 2007-Aug

M3 - Journal article

C2 - 17912037

SN - 1538-4101

VL - 6

SP - 2697

EP - 2705

JO - Cell Cycle

JF - Cell Cycle

IS - 21

ER -