The onset of p53-dependent apoptosis plays a role in terminal differentiation of human normoblasts

Shoshana Peller*, Jenny Frenkel, Tsvee Lapidot, Joy Kahn, Naomi Rahimi-Levene, Rivka Yona, Lior Nissim, Naomi Goldfinger, Dan J. Sherman, Varda Rotter

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


The p53 tumor suppressor gene was found to play a role in the differentiation of several tissue types. We report here that p53-dependent apoptosis plays a role in the final stages of physiological differentiation of normoblasts, resulting in nuclear condensation and expulsion without cell death. Blood samples of healthy newborns, cord blood as well as bone marrow, were analysed for apoptosis by TUNEL and p53 expression by immunostaining. While some samples exhibited simultaneously several distinct patterns of apoptosis, such as perinuclear, diffused nuclear or nuclear apoptotic bodies, others presented a single defined pattern. Overexpression of p53 protein was detected in normoblasts exhibiting either perinuclear or diffused nuclear p53, corresponding to the nuclear apoptotic pattern in the same sample. Similar results were also evident with colonies cultivated for 12-14 days in culture. Differentiated erythroid colonies exhibited overexpression of p53 and positive TUNEL staining only in the normoblasts. We further examined the state of caspase 3/7 and observed a decrease of this activated enzyme during erythroid differentiation in culture. This study suggests a novel role for apoptosis in normoblast differentiation where nuclear degradation occurs with a delay in the actual cell death. A pivotal role for the p53-dependent apoptosis in the erythroid lineage development is implied. However, this apoptotic process is not fully executed because of the exhaustion in caspase 3/7 and thus cells are diverted towards final stages of differentiation.

Original languageAmerican English
Pages (from-to)4648-4655
Number of pages8
Issue number30
StatePublished - 24 Jul 2003
Externally publishedYes

Bibliographical note

Funding Information:
The excellent technical assistance of Mrs Miri Rotschild is acknowledged. This study was supported by a grant from the Israel Cancer Association (SP) and in part by grants from the Israel–USA Binational Science Foundation (BSF) (VR), and the Kadoori Foundation VR. VR is the incumbent of the Norman and Helen Asher Professorial Chair in Cancer Research at the Weizmann Institute.


  • Apoptosis
  • Differentiation
  • Erythropoiesis
  • p53


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