Rhabdomyosarcoma, one of the most common solid tumors of childhood, is believed to arise as a result of a regulatory abnormality of the growth and differentiation of myogenic precursor cells. Despite the expression of myogenic basic-helix-loop-helix proteins of the MyoD family, rhabdomyosarcoma cells fail to withdraw from the cell cycle and are unable to differentiate into muscle cells. The OBJECTIVE of this research proposal is to investigate the molecular mechanisms that prevent differentiation in human embryonal rhabdomyosarcoma (RD) cells. By applying combined molecular and biochemical approaches, we hope to understand how regulatory defects could occur at multiple steps of the muscle differentiation program and find clues to the origin of rhabdomyosarcomas.
The SPECIFIC AIMS are: (I) Identify the factors that prevent MyoD from activating a subset of promoters in RD cells using chromatin immuno-precipitation assays; (II) Characterize post-translational modifications and their functionality on E2A proteins using mutagenesis and protein-protein interaction assays; (III) Identify and characterize RD-specific alterations in the MyoD- associated transcriptional complex by Tandem Affinity Purification and tandem mass spectrometry. ? ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32CA117622-01A1
Application #
7113475
Study Section
Special Emphasis Panel (ZRG1-F09-S (20))
Program Officer
Lohrey, Nancy
Project Start
2006-09-01
Project End
2009-08-31
Budget Start
2006-09-01
Budget End
2007-08-31
Support Year
1
Fiscal Year
2006
Total Cost
$53,992
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109
Yang, Zhihong; MacQuarrie, Kyle L; Analau, Erwin et al. (2009) MyoD and E-protein heterodimers switch rhabdomyosarcoma cells from an arrested myoblast phase to a differentiated state. Genes Dev 23:694-707