Biomedical subjects

Cornelis Murre

Publications and source records attributed to Cornelis Murre.

3 recordsLinked to original sources

PubMed2002

Disruption of pre-TCR expression accelerates lymphomagenesis in E2A-deficient mice.

The helix-loop-helix proteins E47 and E12, which are encoded by the E2A gene, regulate several stages of T cell development. In addition, mice deficient for E2A are highly susceptible to thymic lymphoma. Here we report that the development of lymphoma in E2A-deficient mice did not require pre- and recombinase-activating gene expression. Rather, we found that, whereas illegitimate DNA rearrangement did not play a major role in the development of these lymphomas, defects that prevented pre-T cell antigen receptor expression tended to accelerate lymphomagenesis in E2A-deficient mice. These data and previous observations also provide insight into the role of Notch in lymphoma development. Specifically, we propose that Notch activation indirectly modulates E2A activity through induction of pre-Talpha expression, ultimately leading to the development of lymphoma.

Animals↗

PubMed2002

IL-7Ralpha and E47: independent pathways required for development of multipotent lymphoid progenitors.

Mice that lack the transcription factors encoded by the E2A gene or the receptor for interleukin 7 (IL-7R) have severe overlapping defects in lymphocyte development. Here, we show that E2A proteins are required for the survival of early T-lineage cells; however, they function through a pathway that is distinct from the survival pathway initiated by IL-7R signaling. While E2A proteins are required to suppress caspase 3 activation, ectopic expression of the anti-apoptotic protein Bcl-2 is not sufficient to overcome the lymphopoietic defects observed in the absence of E2A. Remarkably, mice that lack both IL-7Ralpha and E47 display a synergistic decrease in the number of T-cell, NK-cell and multipotent progenitors in the thymus, indicating that these distinct survival pathways converge to promote the development of multipotent lymphoid progenitors.

Animals↗

PubMed2001

E protein function in lymphocyte development.

Lymphocytes arise from hematopoietic stem cells through the coordinated action of transcription factors. The E proteins (E12, E47, HEB and E2-2) have emerged as key regulators of both B and T lymphocyte differentiation. This review summarizes the current data and examines the various functions of E proteins and their antagonists, Id2 and Id3, throughout lymphoid maturation. Beyond an established role in B and T lineage commitment, E proteins continue to be essential at subsequent stages of development. E protein activity regulates the expression of surrogate and antigen receptor genes, promotes Ig and TCR rearrangements, and coordinates cell survival and proliferation with developmental progression in response to TCR signaling. Finally, this review also discusses the role of E47 as a tumor suppressor.

Animals↗