The tumor suppressor protein Fhit. A novel interaction with tubulin

Asish R. Chaudhuri, Israr A. Khan, Veena Prasad, Angela K. Robinson, Richard F. Ludueña, Larry D. Barnes

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

FHIT (fragile histidine triad) is a candidate human tumor suppresser gene located at chromosome 3p14.2, a location that encompasses the FRA3B chromosomal fragile site. Aberrant transcripts have been detected in a variety of primary tumors, and homozygous deletions in the FHIT locus have been detected in different tumor cell lines. The gene product Fhit in vitro possesses the ability to hydrolyze diadenosine 5',5'''-P1,P3-triphosphate (Ap3A). The mechanism of action of Fhit as a tumor suppresser is unknown. Because the tubulin-microtubule system plays an important role in cell division and cell proliferation, we investigated the interaction between wild-type Fhit or mutant Fhit (H96N) and tubulin in vitro. The mutant form of Fhit (H96N) lacks Ap3A hydrolase activity but retains tumor suppresser activity. We found that both wild-type and mutated forms of Fhit bind to tubulin strongly and specifically with K(d) values of 1.4 and 2.1 μM, respectively. Neither wild-type nor mutant Fhit cause nucleation or formation of microtubules, but in the presence of microtubule-associated proteins, both wild-type and mutant Fhit promote assembly to a greater extent than do microtubule-associated proteins alone, and the microtubules formed appear normal by electron microscopy. Our results suggest the possibility that Fhit may exert its tumor suppresser activity by interacting with microtubules and also indicate that the interaction between Fhit and tubulin is not related to the Ap3A hydrolase activity of Fhit.

Original languageEnglish (US)
Pages (from-to)24378-24382
Number of pages5
JournalJournal of Biological Chemistry
Volume274
Issue number34
DOIs
StatePublished - Aug 20 1999

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'The tumor suppressor protein Fhit. A novel interaction with tubulin'. Together they form a unique fingerprint.

  • Cite this

    Chaudhuri, A. R., Khan, I. A., Prasad, V., Robinson, A. K., Ludueña, R. F., & Barnes, L. D. (1999). The tumor suppressor protein Fhit. A novel interaction with tubulin. Journal of Biological Chemistry, 274(34), 24378-24382. https://doi.org/10.1074/jbc.274.34.24378