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Transcription factor SCL is required for c-kit expression and c-Kit function in hemopoietic cells
1Clinical Research Institute of Montreal, Montréal, Quebec H2W 1R7, Canada.
The Journal of Experimental Medicine
|August 4, 1998
Summary
The transcription factor SCL is essential for hemopoietic cell survival by regulating c-Kit. SCL controls c-Kit expression, which is vital for stem cell factor signaling and cell survival.
Area of Science:
- Hematology
- Molecular Biology
- Cell Biology
Background:
- Stem cell factor (SF) is crucial for hemopoietic cell survival.
- The transcription factor SCL/Tal1 expression correlates with c-Kit receptor expression.
- SCL's role upstream of c-Kit in hemopoietic cells requires investigation.
Purpose of the Study:
- To determine if SCL functions upstream of c-Kit.
- To investigate the role of SCL in regulating c-Kit expression and SF-dependent cell survival.
Main Methods:
- Modulation of SCL function using antisense (as-SCL) and dominant-negative (dn-SCL) constructs in TF-1 cells.
- Analysis of SCL DNA binding activity, apoptosis suppression, c-kit mRNA and protein levels.
- Rescue experiments with SCL or c-kit overexpression.
- Enforced SCL expression in Ba/F3 cells.
Main Results:
- Impaired SCL activity reduced c-Kit levels and SF-dependent survival.
- SCL overexpression rescued c-kit expression and SF responsiveness.
- Ectopic c-Kit expression restored SF responsiveness in as-SCL cells.
- Enforced SCL expression induced c-Kit and SF responsiveness in Ba/F3 cells.
Conclusions:
- c-Kit is a downstream target of the transcription factor SCL.
- SCL is required for c-Kit-dependent hemopoietic cell survival.
- SCL plays a critical role in regulating stem cell factor signaling pathways.