An inhibitor domain in c-Fos regulates activation domains containing the HOB1 motif.

Brown, Helen; Sutherland, J A; Cook, Alistair; Bannister, Andrew J.; Kouzarides, Tony

doi:10.1002/j.1460-2075.1995.tb06982.x

Cited by 43 publications

(34 citation statements)

References 43 publications

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“…Such inhibitor activity has been described for a number of transcription factors (Gashler et al, 1993;Brown et al, 1995;Nerlov and Zi , 1994;Dubendor et al, 1992). However, certain features exhibited by HBP1 (its masked activation domain and RB binding characteristics) are very reminiscent of the viral transcription factor E1A (Figure 8).…”

Section: Discussionmentioning

confidence: 75%

The HMG-box transcription factor HBP1 is targeted by the pocket proteins and E1A

et al. 1997

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A yeast two-hybrid screen has identi®ed HBP1 as a transcription factor capable of interacting with the pocket protein family. We show that HBP1 can interact with one of these, RB, both in vitro and in mammalian cells. Two distinct RB binding sites are present within HBP1 ± a high a nity binding site, mediated by an LXCXE motif and a separate low a nity binding site present within an activation domain. GAL4-fusion experiments indicate that HBP1 contains a masked activation domain. Deletion of two independent N-and C-terminal inhibitor domains unmasks an activation domain which is 100-fold more active than the full length protein. The released activation capacity is repressed by RB, p130 and p107. In addition, E1A can repress the activity of HBP1 via conserved region 1 sequences in a manner independent of the CBP coactivator. We show by stable expression in NIH3T3 cells that HBP1 has the capacity to induce morphological transformation of cells in culture.

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Section: Discussionmentioning

confidence: 75%

The HMG-box transcription factor HBP1 is targeted by the pocket proteins and E1A

et al. 1997

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“…The C-terminal domain of Fos contains three Fos activation modules (see Figure 4a), which have been shown to cooperate with each other to activate transcription (Brown et al, 1995). These regions mediate direct interaction of Fos with the TATAbox-binding protein (TBP) and the transcription factor IID (TFIID) complex, which is an important step for activation of transcription by Fos (Brown et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, although the exact mechanism of the stimulation of GAL4/Fos activity by PML is not clear at this point, it can be postulated that PML may stabilize interaction of Fos with its co-activator CBP, the TBP/TFIID complex, or both, which involve its Cterminal domain. However, the possible sequestration of a co-inhibitor of Fos by PML cannot be ignored (Brown et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

“…However, when targeted to DNA through a heterologous DNAbinding domain (DBD) such as that of GAL4, Fos can strongly stimulate transcription from GAL4 target promoters (Sutherland et al, 1992). The GAL4/Fos fusion protein has also been used in several studies to investigate the functional interaction of Fos with other proteins such as CBP (Sutherland et al, 1992;Brown et al, 1995). Therefore, a similar plasmid encoding the Fos protein linked to the DBD of GAL4 (amino acids 1 ± 47) (Sutherland et al, 1992) was used to analyse the activity of the GAL4/Fos fusion on GAL4 target reporter plasmids in the presence of PML or PMLRARa.…”

Section: Pml and Pmlrara Induce Fos-mediated Transcriptional Activitymentioning

confidence: 99%

“…Expression of PML had no signi®cant e ect on the activity of the mutants carrying only the N-terminal domain of Fos, GAL4/Fos (1 ± 81) and GAL4/Fos (1 ± 142), containing Fos amino acids 1 ± 81 and 1 ± 142, respectively. The low activity of GAL4/Fos (1 ± 142), which is due to the presence of an inherent inhibitory domain referred to as ID1 (Brown et al, 1995), was slightly reduced in the presence of PML. Interestingly, the activity of a C-terminal half mutant of Fos containing the dimerization domain (bzip) and the adjacent C-terminal sequences, GAL4/Fos (143 ± 380), was signi®cantly induced in the presence of PML at a level comparable with that of the GAL4/Fos construct (compare lanes 5 and 2 in Figure 4a).…”

Section: Identi®cation Of Domains Of Pml and Fos Necessary For Their mentioning

confidence: 99%

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Modulation of Fos-mediated AP-1 transcription by the promyelocytic leukemia protein

et al. 1998

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The growth and transformation suppressor function of promyelocytic leukemia (PML) protein are disrupted in acute promyelocytic leukemia (APL) as a result of its fusion to the RARa gene by t(15;17) translocation. There is signi®cant sequence homology between the dimerization domain of PML and the Fos family of proteins, which imply that PML may be involved in AP-1 activity. Here we show that PML can cooperate with Fos to stimulate its AP-1-mediated transcriptional activity. Cotransfection of PML with GAL4/Fos strongly induced Fos-mediated activation of GAL4-responsive reporters, indicating a functional interaction between Fos and PML in vivo. Deletion analysis of Fos and PML demonstrated that the intact C-terminal domain of Fos (containing the dimerization domain), and the RING-®nger, B1 box and nuclear localization domains of PML are involved in the cooperative activity of Fos and PML. Immunoprecipitation and electrophoretic mobility shift assay showed that PML is associated with the AP-1 complex. PMLRARa was also found to enhance the transcriptional activity of GAL4/Fos. The addition of retinoic acid abrogated the PMLRARa, but not PML-induced stimulation of GAL4/Fos activity in a dose-dependent manner. This study demonstrated that PML is involved in the AP-1 complex and can modulate Fos-mediated transcriptional activity, which may contribute to its growth suppressor function.

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CBP-induced stimulation of c-Fos activity is abrogated by E1A.

1995

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The CBP protein stimulates transcription of cAMP‐responsive genes by binding to the phosphorylated activation domain of the CREB transcription factor. Here we show that CBP stimulates transcription of Fos/Jun activity in F9 cells and that this response of mediated, at least partly, via c‐Fos. We show that CBP binds c‐Fos in a phosphorylation‐independent manner in vitro, using a domain distinct from that required to bind CREB. When this CBP domain is linked to the activation domain of VP16 it can stimulate GAL4‐Fos activity in vivo. The domain of CBP that binds c‐Fos is also used to contact the E1A protein. We therefore asked whether the documented repression of AP1 activity by E1A is due to sequestration of CBP from c‐Fos. We show that E1A 12S can repress c‐Fos activation functions. The use of E1A mutants indicates that binding of CBP, but not RB, to E1A is essential for E1A‐mediated repression. These data support a model whereby E1A can modulate AP1 activity by directly competing for the CBP co‐activator protein.

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An inhibitor domain in c-Fos regulates activation domains containing the HOB1 motif.

Cited by 43 publications

References 43 publications

The HMG-box transcription factor HBP1 is targeted by the pocket proteins and E1A

The HMG-box transcription factor HBP1 is targeted by the pocket proteins and E1A

Modulation of Fos-mediated AP-1 transcription by the promyelocytic leukemia protein

CBP-induced stimulation of c-Fos activity is abrogated by E1A.

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