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  • The EMBO Journal (2002) 21, 653 - 664
  • doi:10.1093/emboj/21.4.653

The centrosomal protein TACC3 is essential for hematopoietic stem cell function and genetically interfaces with p53-regulated apoptosis

Roland P. Piekorz1,2, Angelika Hoffmeyer1,2,7, Christopher D. Duntsch2,3,7, Catriona McKay1,2,7, Hideaki Nakajima2,4,7, Veronika Sexl2,5, Linda Snyder1,2, Jerold Rehg6 and James N. Ihle1,2,3

  1. Howard Hughes Medical Institute, St Jude Children's Research Hospital, Memphis, TN 38105, USA
  2. Department of Biochemistry, St Jude Children's Research Hospital, Memphis, TN 38105, USA
  3. Department of Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38105, USA
  4. Present address: Blood Center, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160, Japan
  5. Present address: Department of Pharmacology, University of Vienna, A-1090 Vienna, Austria
  6. Department of Pathology, St Jude Children's Research Hospital, Memphis, TN 38063, USA
  7. A.Hoffmeyer, C.D.Duntsch, C.McKay and H.Nakajima contributed equally to this work

Correspondence to:

James N. Ihle, E-mail: james.ihle@stjude.org

Received 26 September 2001; Accepted 20 December 2001; Revised 19 December 2001

TACC3 is a centrosomal/mitotic spindle-associated protein that is highly expressed in a cell cycle-dependent manner in hematopoietic lineage cells. During embryonic development, TACC3 is expressed in a variety of tissues in addition to the hematopoietic lineages. TACC3 deficiency causes an embryonic lethality at mid- to late gestation involving several lineages of cells. Hematopoietic stem cells, while capable of terminal differentiation, are unable to be expanded in vitro or in vivo in reconstitution approaches. Although gross alterations in centrosome numbers and chromosomal segregation are not observed, TACC3 deficiency is associated with a high rate of apoptosis and expression of the p53 target gene, p21Waf1/Cip1. Hematopoietic stem cell functions, as well as deficiencies in other cell lineages, can be rescued by combining the TACC3 deficiency with p53 deficiency. The results support the concept that TACC3 is a critical component of the centrosome/mitotic spindle apparatus and its absence triggers p53-mediated apoptosis.

  • Keywords:

    • apoptosis,
    • centrosome,
    • hematopoiesis,
    • p53,
    • TACC3