[Frontiers in Bioscience 16, 105-115, January 1, 2011]

TGF-beta-dependent and -independent roles of STRAP in cancer

Jennifer Elisabeth Reiner2, Pran K. Datta1,2

Departments of 1Surgery, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA, 2Cancer Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. TGF-beta signaling
3.1. The Smad-dependent and Smad-independent TGF-beta pathways 3.2. STRAP inhibits Smad-dependent TGF-beta signaling
4. STRAP influences TGF-beta and non-TGF-beta pathways through interaction with other proteins
4.1. STRAP promotes signaling through the PI3K pathway by associating with PDK-1
4.2. The Tumor suppressor NM23-H1 physically interacts with STRAP
4.3. STRAP modulates the function of Ewing Sarcoma protein
4.4. STRAP association with ASK1 negatively regulates activation of MAPK stress pathways
5. STRAP is involved in maintaining mesenchymal morphology of fibroblasts
6. The role of STRAP in mRNA splicing and cap-independent translation
7. Clinical Significance and targeted inhibition of STRAP
8. Conclusion
9. Acknowledgements
10. References

1. ABSTRACT

The serine-threonine kinase receptor-associated protein (STRAP) was initially identified as a putative inhibitor of the canonical TGF-beta signaling pathway. Because the Smad-dependent TGF-beta pathway negatively regulates cellular growth, early functional studies suggested that STRAP behaves as an oncogene. Indeed, a correlation between STRAP overexpression and various cancers has been identified. With the emergence of new studies on the biological function of STRAP, it is becoming clear that STRAP regulates several distinct cellular processes and modulates multiple signaling pathways. While STRAP itself does not possess enzymatic activity, it appears that STRAP influences biological processes through associations with cellular proteins. In this review, we will describe the TGF-beta-dependent and -independent functions of STRAP and provide a context for the significance of STRAP activity in the development of cancer.