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Updated: Aug 12, 2026
Expression Analysis of Mammalian Linker-histone Subtypes
Published on: March 19, 2012
[HS1 and EMS1]
H He1
1Ludwig Institute for Cancer Research, Melbourne.
Insights
Hematopoiesis-specific protein HS1 and EMS1/cortactin act as tumor suppressors. HS1
Area of Science:
- Molecular Oncology
- Cell Biology
- Biochemistry
Background:
- HS1 and EMS1/cortactin are cytoskeletal SH3 proteins.
- EMS1 gene amplification in mammary tumors initially suggested a proto-oncogene role.
- Cytoskeletal proteins play crucial roles in cell structure and function.
Purpose of the Study:
- To investigate the oncogenic potential of HS1 and EMS1.
- To determine the functional domains of HS1 required for its anti-oncogenic activity.
- To compare the structural and functional similarities between HS1 and EMS1.
Main Methods:
- Expression analysis of HS1 and EMS1 in mammary tumors.
- Functional assays using oncogenic Ras mutants.
- Site-directed mutagenesis to identify critical domains for anti-oncogenicity.
- Sequence homology analysis between HS1 and EMS1.
Main Results:
- Full-length HS1 suppresses malignant transformation induced by oncogenic Ras.
- HS1's anti-oncogenicity depends on its SH3 domain, actin-binding motifs, and specific tyrosine residues.
- EMS1 shares significant sequence identity with HS1 in critical functional domains.
- Overexpression of EMS1 inhibits, rather than promotes, normal cell growth.
Conclusions:
- HS1 functions as a tumor suppressor, contrary to initial hypotheses about EMS1.
- EMS1 likely also acts as a tumor suppressor, sharing functional domains with HS1.
- Actin-binding is essential for the tumor-suppressive activity of HS1, a novel finding for actin-binding tumor suppressors.
Abstract:
Both HS1 (hematopoiesis specific) and EMS1/ cortactin belong to a growing family of cytoskeletal SH3 proteins. Most proteins in this family, except for alpha-spectrin, contain a single SH3 domain at the C-terminus, and an F-actin binding domain (s) at the N-terminus. The main reason why EMS1 initially attracted great attention among molecular oncologists is the amplification and over-expression of EMS1 gene in mammary tumors. However, our recent study on HS1 suggests that EMS1 is a tumor suppressor rather than a proto-oncoprotein. First of all, full-length HS1 of 486 amino acids suppresses the malignant transformation caused by oncogenic Ras mutants such as v-Ha-Ras. Second, for its anti-oncogenicity, HS1 requires the C-terminal SH3 domain, and the N-terminal actin-binding motifs, in addition to two phosphorylatable Tyr residues at positions 378 and 397. Third, EMS1 shares with HS1 80% sequence identity in the C-terminal SH3 domain, and 70% identity in the N-terminal actin-binding motifs, and contains these two Tyr residues, all of which are required for the anti-oncogenicity of HS1. Lastly, overexpression of EMS1 does not transform normal cells, and rather disfavors their growth. Among several actin-binding tumor suppressors, HS1 is the first tumor suppressor whose actin-binding has been shown to be essential for its anti-oncogenicity.
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