Cyclin E/cdk2 and cyclin A/cdk2 kinases associate with p107 and E2F in a temporally distinct manner.

Lees, Emma; Faha, Barbara; Dulić, Vjekoslav; Reed, Steven I.; Harlow, E

doi:10.1101/gad.6.10.1874

Cited by 436 publications

(331 citation statements)

References 68 publications

(96 reference statements)

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“…This ®nding is consistent with immunoblotting results, which show a higher proportion of hypophosphorylated p107 in the ®ber cells than in the epithelial cells. Complexes containing p107 have previously been associated with cycling cells, where they are most abundant during S phase (Shirodkar et al, 1992;Lees et al, 1992;Kiess et al, 1995). Such p107 complexes generally also contain Cdk2 and cyclin E or A (Lees et al, 1992).…”

Section: Discussionmentioning

confidence: 98%

“…Complexes containing p107 have previously been associated with cycling cells, where they are most abundant during S phase (Shirodkar et al, 1992;Lees et al, 1992;Kiess et al, 1995). Such p107 complexes generally also contain Cdk2 and cyclin E or A (Lees et al, 1992). We have not yet tested for the presence of cyclins or Cdks in the p107/E2F complexes from lens ®ber cells.…”

Section: Discussionmentioning

confidence: 98%

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pRb and p107 regulate E2F activity during lens fiber cell differentiation

et al. 1998

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During growth arrest and di erentiation, activity of the E2F family of transcription factors is inhibited by interactions with pRb and the related proteins, p107 and p130. To determine which members of the E2F and pRb families may contribute to growth arrest as lens epithelial cells di erentiate into ®ber cells, we examined the expression of individual E2F species and characterized the E2F protein complexes formed in rat lens epithelia and ®bers. RT/PCR detected all ®ve known members of the E2F family in lens epithelial cells, but only E2F-1, E2F-3, and E2F-5 in ®ber cells. Proteins extracted from lens epithelia of newborn rats formed at least two speci®c complexes with an E2F consensus oligonucleotide. Proteins from lens ®ber cells formed three speci®c complexes, one of which comigrated with an epithelial cell complex. Incubation of epithelial and ®ber cell extracts with an antibody speci®c for p107 demonstrated that two ®ber cell complexes and one epithelial cell complex contained p107. Although the remaining ®ber cell complex did not react with antibodies to pRb or p130 in this assay, a strong reaction with pRb antibody was observed when the electromobility shifted complexes were subsequently immunoblotted (shift/Western assay). Immunocytochemistry con®rmed that pRb protein is present in the nuclei of both epithelial cells and ®ber cells. Immunoblotting of whole cell extracts with pRb antibody showed multiple, phosphorylated forms of pRb in the epithelial cells, but predominantly hypophosphorylated pRb in the ®ber cells. None of the complexes formed with E2F were recognized exclusively by the p130 antibody, although the previously identi®ed p107 complexes reacted weakly. The absence of p130/E2F complexes was correlated with the presence of multiple ubiquitinated forms of p130, especially in the ®ber cells. Thus, although p130/E2F complexes are implicated in the terminal di erentiation of many cell types, in di erentiating lens ®ber cells pRb and p107 seem to be the primary regulators of E2F activity.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 98%

pRb and p107 regulate E2F activity during lens fiber cell differentiation

et al. 1998

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“…In addition, pRb, but not p107, is thought to be a substrate for cyclin A/cdk2 and cyclin E/cdk2 (Hinds et al, 1992;Dowdy et al, 1993;Ewen et al, 1993;Beijersbergen et al, 1995). It is somewhat enigmatic that even though p107 and p130 do not appear to be phosphorylated by cyclin A/cdk2 and cyclin E/cdk2, both pocket proteins can form stable complexes with cyclin A/cdk2 and E/cdk2 through a domain within the pocket called the spacer (Lees et al, 1992;Shirodkar et al, 1992;Li et al, 1993a;Zhu et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Functional interaction between a novel protein phosphatase 2A regulatory subunit, PR59, and the retinoblastoma-related p107 protein

1999

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The proteins of the retinoblastoma family are potent inhibitors of cell cycle progression. It is well documented that their growth-inhibitory activity can be abolished by phosphorylation on serine and threonine residues by cyclin dependent kinases. In contrast, very little is known about the dephosphorylation of retinoblastoma-family proteins. We report here the isolation, by virtue of its ability to associate with p107, of a novel Protein Phosphatase 2A (PP2A) regulatory subunit, named PR59. PR59 shares sequence homology with a known regulatory subunit of PP2A, PR72, but di ers from PR72 in its expression pattern and its functional properties. We show that PR59 co-immunoprecipitates with the PP2A catalytic subunit, indicating that PR59 is a genuine component of PP2A holo-enzymes. In vivo, PR59 associates speci®cally with p107, but not with pRb. Elevated expression of PR59 results in dephosphorylation of p107, but not of pRb, and inhibits cell proliferation by causing cells to accumulate in G1. These data support a model in which the distinct PP2A regulatory subunits act to target the PP2A catalytic subunit to speci®c substrates and suggest a role for PP2A in regulation of p107.

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“…In addition to the interactions with the D cyclins, p107 and p130 stably interact with cyclin A/cdk2 and cyclin E/cdk2 complexes in vivo and in vitro Faha et al, 1992Faha et al, , 1993Lees et al, 1992;Hannon et al, 1993;Li et al, 1993;Peeper et al, 1993). This property is not held in common with pRB and the signi®cance of this di erence remains unclear.…”

Section: Introductionmentioning

confidence: 99%