The Cbl interactome and its functions

  title={The Cbl interactome and its functions},
  author={Mirko H. H. Schmidt and Ivan Dikic},
  journal={Nature Reviews Molecular Cell Biology},
Cbl proteins are ubiquitin ligases and multifunctional adaptor proteins that are implicated in the regulation of signal transduction in various cell types and in response to different stimuli. Cbl-associated proteins can assemble together at a given time or space inside the cell, and such an interactome can form signal competent networks that control many physiological processes. Dysregulation of spatial or temporal constraints in the Cbl interactome results in the development of human… 

Ubiquitin and NEDD8: Brothers in Arms

Ubiquitin and NEDD8 share the same E3 ligase, Cbl, and are recognized by identical components of the endocytic sorting machinery, which introduces additional complexity to the current view of Ub signaling pathways.

The Cbl family proteins: Ring leaders in regulation of cell signaling

This review will endeavor to provide a summary of current studies focused on the effects of Cbl proteins on various biological processes and the mechanism of these effects.

Regulation of immune system development and function by Cbl‐mediated ubiquitination

The research progress on the roles of the Cbl family of E3 ubiquitin ligases in the development and function of lymphocytes and non‐lymphoid cells is updated and the current understanding of the mechanisms used by this family of proteins to co‐ordinately regulate the function of various receptors and transcription factors is highlighted.

Ubiquitin and ubiquitin-like proteins in cancer pathogenesis

The common principles and specific features of ubiquitin and Ubls in the regulation of cancer-relevant pathways are summarized, and new strategies to target Ubiquitin signalling in drug discovery are discussed.

Molecular Pathways: Cbl Proteins in Tumorigenesis and Antitumor Immunity—Opportunities for Cancer Treatment

Improved understanding of how the signaling pathways are dysregulated by these mutations in Cbl has helped to identify potential targets for therapy of myeloid neoplasms.

Cbl- and Nedd4-family ubiquitin ligases: balancing tolerance and immunity

This review will explore how a small group of E3 ubiquitin ligases regulate T cell responses and thus direct adaptive immunity.

Non-proteolytic ubiquitylation in cellular signaling and human disease

This review summarizes the current knowledge and the latest concepts on how non-proteolytic ubiquitylation pathways are involved in cellular signaling and in disease-mediating processes and may advance the understanding of the non-degradative Ubiquitylation process.

Indispensable roles of mammalian Cbl family proteins as negative regulators of protein tyrosine kinase signaling

Recent progress in murine models that are beginning to provide insights into the critical roles of Cbl proteins in physiological pathways are discussed, with important implications in understanding how aberrations of C Bl proteins contribute to oncogenesis.

The protein content of an adaptor protein, STAP-2 is controlled by E3 ubiquitin ligase Cbl.




Cbl signaling networks in the regulation of cell function

It is becoming obvious that temporal and spatial changes in Cbl signaling networks are essential for the control of physiological processes in a variety of cells and organs and that their deregulation can result in the development of human diseases.

E3 ubiquitin ligases as T cell anergy factors

The relationship between the ubiquitination of select components of the antigen-sensing signaling apparatus in T cells and the development and maintenance of the clonal anergy state is discussed.

Adaptor proteins in lymphocyte activation.

CIN85/CMS family of adaptor molecules

  • I. Dikic
  • Biology, Chemistry
    FEBS letters
  • 2002

Characterization of the CIN85 adaptor protein and identification of components involved in CIN85 complexes.

The data suggest that CIN85 may serve for regulation of various signaling events through formation of its diverse complexes throughformation of its SH3 domains.

TULA: an SH3- and UBA-containing protein that binds to c-Cbl and ubiquitin

The study indicates that TULA counters the inhibitory effect of c-Cbl on protein tyrosine kinases and, thus, may be involved in the regulation of biological effects of c.Cbl.

When ubiquitin meets ubiquitin receptors: a signalling connection

It is proposed that monoubiquitylation is rapidly induced by signalling events and allows the establishment of protein–protein interactions between monoubquitylated proteins and partners that contain distinct ubiquitin-binding domains.

Cbl: many adaptations to regulate protein tyrosine kinases

Responses to extracellular stimuli are often transduced from cell-surface receptors to protein tyrosine kinases which, when activated, initiate the formation of protein complexes that transmit

Tal, a Tsg101-specific E3 ubiquitin ligase, regulates receptor endocytosis and retrovirus budding.

It is concluded that Tal regulates a Tsg101-associated complex responsible for the sorting of cargo into cytoplasm-containing vesicles that bud at the multivesicular body and at the plasma membrane.

WW Domain HECT E3s Target Cbl RING Finger E3s for Proteasomal Degradation*

It is established that two WW domain HECT E3s, Nedd4 and Itch, bind Cbl proteins and target them for proteasomal degradation, and suggested an additional level of regulation for Cbl substrates including protein-tyrosine kinases.