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

Roland P. Piekorz, Angelika Hoffmeyer, Christopher D. Duntsch, Catriona McKay, Hideaki Nakajima, Veronika Sexl, Linda Snyder, Jerold Rehg, James N. Ihle

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)653-664
Number of pages12
JournalEMBO Journal
Volume21
Issue number4
DOIs
Publication statusPublished - 2002 Feb 15
Externally publishedYes

Fingerprint

Centrosome
Spindle Apparatus
Hematopoietic Stem Cells
Stem cells
Apoptosis
p53 Genes
Cell Lineage
Embryonic Development
Cell Cycle
Proteins
Genes
Cells
Tissue
Pregnancy
In Vitro Techniques

Keywords

  • Apoptosis
  • Centrosome
  • Hematopoiesis
  • P53
  • TACC3

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Piekorz, R. P., Hoffmeyer, A., Duntsch, C. D., McKay, C., Nakajima, H., Sexl, V., ... Ihle, J. N. (2002). The centrosomal protein TACC3 is essential for hematopoietic stem cell function and genetically interfaces with p53-regulated apoptosis. EMBO Journal, 21(4), 653-664. https://doi.org/10.1093/emboj/21.4.653

The centrosomal protein TACC3 is essential for hematopoietic stem cell function and genetically interfaces with p53-regulated apoptosis. / Piekorz, Roland P.; Hoffmeyer, Angelika; Duntsch, Christopher D.; McKay, Catriona; Nakajima, Hideaki; Sexl, Veronika; Snyder, Linda; Rehg, Jerold; Ihle, James N.

In: EMBO Journal, Vol. 21, No. 4, 15.02.2002, p. 653-664.

Research output: Contribution to journalArticle

Piekorz, RP, Hoffmeyer, A, Duntsch, CD, McKay, C, Nakajima, H, Sexl, V, Snyder, L, Rehg, J & Ihle, JN 2002, 'The centrosomal protein TACC3 is essential for hematopoietic stem cell function and genetically interfaces with p53-regulated apoptosis', EMBO Journal, vol. 21, no. 4, pp. 653-664. https://doi.org/10.1093/emboj/21.4.653
Piekorz, Roland P. ; Hoffmeyer, Angelika ; Duntsch, Christopher D. ; McKay, Catriona ; Nakajima, Hideaki ; Sexl, Veronika ; Snyder, Linda ; Rehg, Jerold ; Ihle, James N. / The centrosomal protein TACC3 is essential for hematopoietic stem cell function and genetically interfaces with p53-regulated apoptosis. In: EMBO Journal. 2002 ; Vol. 21, No. 4. pp. 653-664.
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