The capacity of polyomavirus enhancer binding protein 2αB (AML1/Cbfa2) to stimulate polyomavirus DNA replication is related to its affinity for the nuclear matrix

Lin Feng Chen, Kosei Ito, Yota Murakami, Yoshiaki Ito

Research output: Contribution to journalArticlepeer-review

Abstract

The nuclear matrix is thought to play an important role in the DNA replication of eukaryotic cells, although direct evidence for such a role is still lacking. A nuclear matrix-associated transcription factor, polyomavirus (Py) enhancer binding protein 2αB1 (PEBP2αB1) (AML1/Cbfa2), was found to stimulate Py replication through its cognate binding site. The minimal replication activation domain (RAD) was identified between amino acid (aa) 302 and aa 371 by using a fusion protein containing the GALA DNA binding domain (GAL4-RAD). In addition, the region showed affinity for the nuclear matrix and, on the basis of competition studies, binding activity for one or more proteins involved in the initiation of Py DNA replication. A leukemogenic chimeric protein, AML1/ETO(MTG8), which does not contain this region of PEBP2αB1/AML1, was also localized in the nuclear matrix fraction and competed for nuclear matrix association with PEBP2αB1 and GAL4-RAD. Moreover, AML1/ETO inhibited Py DNA replication stimulated by PEBP2αBI and GAL4-RAD. The inhibition was specific for replication mediated by PEBP2αB1 and GAL4-RAD, and proportional to the degree of loss of these activators from the nuclear matrix, suggesting a requirement for nuclear matrix targeting in the stimulation of Py DNA replication by RAD. These results are the first to suggest a molecular link between the initiation of DNA replication and the nuclear matrix compartment.

Original languageEnglish (US)
Pages (from-to)4165-4176
Number of pages12
JournalMolecular and cellular biology
Volume18
Issue number7
DOIs
StatePublished - Jul 1998
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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