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The 32-kilodalton subunit of replication protein A interacts with menin, the product of the MEN1 tumor suppressor gene.

Menin is a 70-kDa protein encoded by MEN1, the tumor suppressor gene disrupted in multiple endocrine neoplasia type 1. In a yeast two-hybrid system based on reconstitution of Ras signaling, menin was found to interact with the 32-kDa subunit (RPA2) of replication protein A (RPA), a heterotrimeric protein required for DNA replication, recombination, and repair. The menin-RPA2 interaction was confirmed in a conventional yeast two-hybrid system and by direct interaction between purified proteins. Menin-RPA2 binding was inhibited by a number of menin missense mutations found in individuals with multiple endocrine neoplasia type 1, and the interacting regions were mapped to the N-terminal portion of menin and amino acids 43 to 171 of RPA2. This region of RPA2 contains a weak single-stranded DNA-binding domain, but menin had no detectable effect on RPA-DNA binding in vitro. Menin bound preferentially in vitro to free RPA2 rather than the RPA heterotrimer or a subcomplex consisting of RPA2 bound to the 14-kDa subunit (RPA3). However, the 70-kDa subunit (RPA1) was coprecipitated from HeLa cell extracts along with RPA2 by menin-specific antibodies, suggesting that menin binds to the RPA heterotrimer or a novel RPA1-RPA2-containing complex in vivo. This finding was consistent with the extensive overlap in the nuclear localization patterns of endogenous menin, RPA2, and RPA1 observed by immunofluorescence.

Pubmed ID: 12509449


  • Sukhodolets KE
  • Hickman AB
  • Agarwal SK
  • Sukhodolets MV
  • Obungu VH
  • Novotny EA
  • Crabtree JS
  • Chandrasekharappa SC
  • Collins FS
  • Spiegel AM
  • Burns AL
  • Marx SJ


Molecular and cellular biology

Publication Data

January 1, 2003

Associated Grants


Mesh Terms

  • Animals
  • Bacterial Proteins
  • Blotting, Western
  • Cell Line
  • Cell Nucleus
  • Chromatography, Gel
  • DNA
  • DNA Damage
  • DNA, Complementary
  • DNA-Binding Proteins
  • G1 Phase
  • Glutathione Transferase
  • HeLa Cells
  • Humans
  • Mice
  • Microscopy, Fluorescence
  • Multiple Endocrine Neoplasia
  • Mutation, Missense
  • Neoplasm Proteins
  • Plasmids
  • Precipitin Tests
  • Protein Binding
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins
  • Recombinant Proteins
  • Replication Protein A
  • S Phase
  • Transfection
  • Two-Hybrid System Techniques