Student news: T-box protein in heart development and disease (InTouch Spring 2008)

MCB_spring08Andre Kulisz, PhD, a postdoctoral fellow in the laboratory of Hans-Georg Simon, PhD, is first author on a paper recently published in the journal Molecular and Cellular Biology. The work is entitled: “An evolutionarily conserved nuclear export signal facilitates cytoplasmic localization of the Tbx5 transcription factor.” During cardiac development, the T-box transcription factor Tbx5 displays dynamic changes in localization from strictly nuclear to both nuclear and cytoplasmic to exclusively cytoplasmic along the actin cytoskeleton in cells coexpressing its binding protein LMP4. The authors identified a functional nuclear export signal sequence in Tbx5 that uses the CRM1 protein to shuttle out of the nucleus. The findings suggest that Tbx5 is using a mechanism for protein relocalization that evolved early in the generation of the T-box protein family, thus setting a new paradigm for nuclear and cytoplasmic functions of T-box proteins during developmental and disease processes.

Based on this work, Kulisz was awarded a postdoctoral fellowship from the American Heart Association for a project titled “The role of nuclear and cytoplasmic localization of the Tbx5 transcription factor in cardiac development and disease.” He will be considering two major questions: What role does Tbx5 protein location in the cell have in forming the proper structures during heart development? How does its location influence behavior at the level of a single cell? Understanding changes in behavior of individual cells will help explain malformations observed in the entire heart.

Simon is assistant professor of Pediatrics at Northwestern University's Feinberg School of Medicine and Bernard L. Mirkin Scholar in the Developmental Biology Program of Children's Memorial Research Center.

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