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Nonmyristoylated Abl proteins transform a factor-dependent hematopoietic cell line
G Q Daley1, R A Van Etten, P K Jackson
1Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142.
Molecular and Cellular Biology
|April 1, 1992
Summary
Myristoylation is not required for Abl proteins to transform hematopoietic cells, unlike fibroblasts. Abl variants can transform lymphoid cells without plasma membrane association, indicating distinct transformation mechanisms.
Area of Science:
- Oncogenic signaling pathways
- Protein modification in cancer
- Hematopoietic cell transformation
Background:
- N-terminal myristoylation facilitates protein association with the plasma membrane.
- This membrane association is crucial for oncogenic Src and Abl proteins transforming fibroblasts.
- P210bcr/abl, lacking myristoylation, transforms hematopoietic cells but not fibroblasts, suggesting myristoylation is dispensable for hematopoietic transformation.
Purpose of the Study:
- To investigate whether myristoylation is essential for Abl variants to transform hematopoietic cells.
- To determine if Abl proteins require plasma membrane association for hematopoietic cell transformation.
- To compare the transformation mechanisms of Abl variants in fibroblasts versus hematopoietic cells.
Main Methods:
- Introduction of point mutations to disrupt myristoylation in v-Abl and c-Abl (delta XB) proteins.
- Assessment of the transforming ability of nonmyristoylated Abl variants on NIH 3T3 fibroblasts.
- Evaluation of the transformation capacity of nonmyristoylated Abl variants on the Ba/F3 lymphoblastoid cell line.
- Analysis of plasma membrane association of nonmyristoylated Abl variants in transformed Ba/F3 cells.
Main Results:
- Nonmyristoylated v-Abl and delta XB Abl proteins failed to transform NIH 3T3 fibroblasts.
- Both nonmyristoylated Abl variants successfully transformed Ba/F3 cells, conferring factor independence and tumorigenicity.
- Transformed Ba/F3 cells expressing nonmyristoylated Abl variants did not exhibit plasma membrane association of the Abl proteins.
- These findings indicate Abl proteins can transform hematopoietic cells independently of membrane association.
Conclusions:
- Abl proteins can transform hematopoietic cells without requiring N-terminal myristoylation or plasma membrane association.
- Distinct functional requirements exist for Abl-mediated transformation of fibroblasts versus hematopoietic cells.
- Myristoylation-independent mechanisms drive Abl transformation in the hematopoietic lineage.