The role of ubiquitylation in signaling by growth factors: implications to cancer.
Cancer cells depend on multiple, locally produced growth factors. Signaling by growth factors entails phosphorylation events, and its termination is determined primarily by endocytosis of growth factor receptor complexes. One group of growth factor receptors frequently implicated in human cancer is the ErbB family of receptor tyrosine kinases. By using ErbB as a prototype, here we review the role of protein ubiquitylation in the process that terminates signaling. Specifically, we concentrate on several adaptor proteins, including c-Cbl and Hgs, to elucidate the complexity of receptor sorting for degradation. Detailed understanding of ubiquitylation control on receptor desensitization may lead to better ways to diagnose and eradicate cancer.
Shtiegman
Keren
K
Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel.
Yarden
Yosef
Y
D000595:Amino Acid Sequence; D000818:Animals; D004705:Endocytosis / Q000502:physiology*; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000378:metabolism*; D011487:Protein Conformation; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D050721:Proto-Oncogene Proteins c-cbl; D017978:Receptors, Growth Factor; D015398:Signal Transduction / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000378:metabolism*
D006133:Growth Substances; D011518:Proto-Oncogene Proteins; D017978:Receptors, Growth Factor; D014452:Ubiquitins; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; C067419:CBL protein, human