Unique roles for E2F1 in the mouse lens in the absence of functional pRB proteins

R. Katherine Hyde, Anne E. Griep

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

PURPOSE. Normal lens fiber cell differentiation requires functional retinoblastoma protein (pRB), because inactivation of this protein results in proliferation and apoptosis in normally postmitotic, differentiating fiber cells. Loss of either E2F1 or -3 can partially rescue the lens phenotype in Rb-deficient mice, implying that these E2Fs may have specific targets in this system. The purpose of this study was to determine what unique role E2F1 may play. METHODS. Expression of E2F family members and target genes was analyzed in the lenses of nontransgenic, E2171-null, αAE7; E2171-sufficient; and αAE7;E2F1-null mice by in situ hybridization, Northern blot analysis, and RT-PCR. RESULTS. In lenses of E2171-null mice, there was no change in the expression of E2F-2 to -5 or their target genes, compared with E21F1-sufficient mice. However, in the lens of αAE7 mice where pRB proteins are inactivated, expression of E2F2 and -3a was increased. The E2F3a increase, but not that of E2F2, was dependent on E2F1. Expression of E2F target genes was increased with expression of E7 and expression of one of these, p19ARF, was E2F1 dependent. CONCLUSIONS. Although in the normal lens there do not appear to be unique roles for E2F1 that cannot be fulfilled by other E2F family members, in the absence of functional pRB proteins, E2F1 is specifically responsible for the increased expression of E2F3a and p19ARF. These findings suggest that E2F1 may be the preferred E2F regulating these target genes in the normal lens.

Original languageEnglish (US)
Pages (from-to)1509-1516
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume43
Issue number5
StatePublished - May 13 2002

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Lenses
Proteins
Genes
Retinoblastoma Protein
Northern Blotting
In Situ Hybridization
Cell Differentiation
Apoptosis
Phenotype
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Unique roles for E2F1 in the mouse lens in the absence of functional pRB proteins. / Hyde, R. Katherine; Griep, Anne E.

In: Investigative Ophthalmology and Visual Science, Vol. 43, No. 5, 13.05.2002, p. 1509-1516.

Research output: Contribution to journalArticle

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abstract = "PURPOSE. Normal lens fiber cell differentiation requires functional retinoblastoma protein (pRB), because inactivation of this protein results in proliferation and apoptosis in normally postmitotic, differentiating fiber cells. Loss of either E2F1 or -3 can partially rescue the lens phenotype in Rb-deficient mice, implying that these E2Fs may have specific targets in this system. The purpose of this study was to determine what unique role E2F1 may play. METHODS. Expression of E2F family members and target genes was analyzed in the lenses of nontransgenic, E2171-null, αAE7; E2171-sufficient; and αAE7;E2F1-null mice by in situ hybridization, Northern blot analysis, and RT-PCR. RESULTS. In lenses of E2171-null mice, there was no change in the expression of E2F-2 to -5 or their target genes, compared with E21F1-sufficient mice. However, in the lens of αAE7 mice where pRB proteins are inactivated, expression of E2F2 and -3a was increased. The E2F3a increase, but not that of E2F2, was dependent on E2F1. Expression of E2F target genes was increased with expression of E7 and expression of one of these, p19ARF, was E2F1 dependent. CONCLUSIONS. Although in the normal lens there do not appear to be unique roles for E2F1 that cannot be fulfilled by other E2F family members, in the absence of functional pRB proteins, E2F1 is specifically responsible for the increased expression of E2F3a and p19ARF. These findings suggest that E2F1 may be the preferred E2F regulating these target genes in the normal lens.",
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N2 - PURPOSE. Normal lens fiber cell differentiation requires functional retinoblastoma protein (pRB), because inactivation of this protein results in proliferation and apoptosis in normally postmitotic, differentiating fiber cells. Loss of either E2F1 or -3 can partially rescue the lens phenotype in Rb-deficient mice, implying that these E2Fs may have specific targets in this system. The purpose of this study was to determine what unique role E2F1 may play. METHODS. Expression of E2F family members and target genes was analyzed in the lenses of nontransgenic, E2171-null, αAE7; E2171-sufficient; and αAE7;E2F1-null mice by in situ hybridization, Northern blot analysis, and RT-PCR. RESULTS. In lenses of E2171-null mice, there was no change in the expression of E2F-2 to -5 or their target genes, compared with E21F1-sufficient mice. However, in the lens of αAE7 mice where pRB proteins are inactivated, expression of E2F2 and -3a was increased. The E2F3a increase, but not that of E2F2, was dependent on E2F1. Expression of E2F target genes was increased with expression of E7 and expression of one of these, p19ARF, was E2F1 dependent. CONCLUSIONS. Although in the normal lens there do not appear to be unique roles for E2F1 that cannot be fulfilled by other E2F family members, in the absence of functional pRB proteins, E2F1 is specifically responsible for the increased expression of E2F3a and p19ARF. These findings suggest that E2F1 may be the preferred E2F regulating these target genes in the normal lens.

AB - PURPOSE. Normal lens fiber cell differentiation requires functional retinoblastoma protein (pRB), because inactivation of this protein results in proliferation and apoptosis in normally postmitotic, differentiating fiber cells. Loss of either E2F1 or -3 can partially rescue the lens phenotype in Rb-deficient mice, implying that these E2Fs may have specific targets in this system. The purpose of this study was to determine what unique role E2F1 may play. METHODS. Expression of E2F family members and target genes was analyzed in the lenses of nontransgenic, E2171-null, αAE7; E2171-sufficient; and αAE7;E2F1-null mice by in situ hybridization, Northern blot analysis, and RT-PCR. RESULTS. In lenses of E2171-null mice, there was no change in the expression of E2F-2 to -5 or their target genes, compared with E21F1-sufficient mice. However, in the lens of αAE7 mice where pRB proteins are inactivated, expression of E2F2 and -3a was increased. The E2F3a increase, but not that of E2F2, was dependent on E2F1. Expression of E2F target genes was increased with expression of E7 and expression of one of these, p19ARF, was E2F1 dependent. CONCLUSIONS. Although in the normal lens there do not appear to be unique roles for E2F1 that cannot be fulfilled by other E2F family members, in the absence of functional pRB proteins, E2F1 is specifically responsible for the increased expression of E2F3a and p19ARF. These findings suggest that E2F1 may be the preferred E2F regulating these target genes in the normal lens.

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