Book contents
- Frontmatter
- Dedication
- Contents
- List of Contributors
- Preface
- Part 1.1 Analytical techniques: analysis of DNA
- Part 1.2 Analytical techniques: analysis of RNA
- Part 2.1 Molecular pathways underlying carcinogenesis: signal transduction
- 10 HER
- 11 The insulin–insulin-like growth-factor receptor family as a therapeutic target in oncology
- 12 TGF-β signaling in stem cells and tumorigenesis
- 13 Platelet-derived growth factor
- 14 FMS-related tyrosine kinase 3
- 15 ALK: Anaplastic lymphoma kinase
- 16 The FGF signaling axis in prostate tumorigenesis
- 17 Hepatocyte growth factor/Met signaling in cancer
- 18 PI3K
- 19 Intra-cellular tyrosine kinase
- 20 WNT signaling in neoplasia
- 21 Ras
- 22 BRAF mutations in human cancer: biologic and therapeutic implications
- 23 Aurora kinases in cancer: an opportunity for targeted therapy
- 24 14-3-3 proteins in cancer
- 25 STAT signaling as a molecular target for cancer therapy
- 26 The MYC oncogene family in human cancer
- 27 Jun proteins and AP-1 in tumorigenesis
- 28 Forkhead box proteins: the tuning forks in cancer development and treatment
- 29 NF-κB and cancer
- Part 2.2 Molecular pathways underlying carcinogenesis: apoptosis
- Part 2.3 Molecular pathways underlying carcinogenesis: nuclear receptors
- Part 2.4 Molecular pathways underlying carcinogenesis: DNA repair
- Part 2.5 Molecular pathways underlying carcinogenesis: cell cycle
- Part 2.6 Molecular pathways underlying carcinogenesis: other pathways
- Part 3.1 Molecular pathology: carcinomas
- Part 3.2 Molecular pathology: cancers of the nervous system
- Part 3.3 Molecular pathology: cancers of the skin
- Part 3.4 Molecular pathology: endocrine cancers
- Part 3.5 Molecular pathology: adult sarcomas
- Part 3.6 Molecular pathology: lymphoma and leukemia
- Part 3.7 Molecular pathology: pediatric solid tumors
- Part 4 Pharmacologic targeting of oncogenic pathways
- Index
- References
24 - 14-3-3 proteins in cancer
from Part 2.1 - Molecular pathways underlying carcinogenesis: signal transduction
Published online by Cambridge University Press: 05 February 2015
- Frontmatter
- Dedication
- Contents
- List of Contributors
- Preface
- Part 1.1 Analytical techniques: analysis of DNA
- Part 1.2 Analytical techniques: analysis of RNA
- Part 2.1 Molecular pathways underlying carcinogenesis: signal transduction
- 10 HER
- 11 The insulin–insulin-like growth-factor receptor family as a therapeutic target in oncology
- 12 TGF-β signaling in stem cells and tumorigenesis
- 13 Platelet-derived growth factor
- 14 FMS-related tyrosine kinase 3
- 15 ALK: Anaplastic lymphoma kinase
- 16 The FGF signaling axis in prostate tumorigenesis
- 17 Hepatocyte growth factor/Met signaling in cancer
- 18 PI3K
- 19 Intra-cellular tyrosine kinase
- 20 WNT signaling in neoplasia
- 21 Ras
- 22 BRAF mutations in human cancer: biologic and therapeutic implications
- 23 Aurora kinases in cancer: an opportunity for targeted therapy
- 24 14-3-3 proteins in cancer
- 25 STAT signaling as a molecular target for cancer therapy
- 26 The MYC oncogene family in human cancer
- 27 Jun proteins and AP-1 in tumorigenesis
- 28 Forkhead box proteins: the tuning forks in cancer development and treatment
- 29 NF-κB and cancer
- Part 2.2 Molecular pathways underlying carcinogenesis: apoptosis
- Part 2.3 Molecular pathways underlying carcinogenesis: nuclear receptors
- Part 2.4 Molecular pathways underlying carcinogenesis: DNA repair
- Part 2.5 Molecular pathways underlying carcinogenesis: cell cycle
- Part 2.6 Molecular pathways underlying carcinogenesis: other pathways
- Part 3.1 Molecular pathology: carcinomas
- Part 3.2 Molecular pathology: cancers of the nervous system
- Part 3.3 Molecular pathology: cancers of the skin
- Part 3.4 Molecular pathology: endocrine cancers
- Part 3.5 Molecular pathology: adult sarcomas
- Part 3.6 Molecular pathology: lymphoma and leukemia
- Part 3.7 Molecular pathology: pediatric solid tumors
- Part 4 Pharmacologic targeting of oncogenic pathways
- Index
- References
Summary
Introduction
14-3-3 proteins constitute a family of acidic α-helical cup-shaped dimers that are ubiquitously expressed in all eukaryotic cells. Well over 200 proteins have been identified as 14-3-3-binding ligands, and many of these proteins have established roles in cell-cycle control, DNA damage responses, growth-factor receptor signaling, regulation of gene expression, metabolism, and apoptosis (1–5; Figure 24.1). Early work that hinted at a connection between protein phosphorylation and 14-3-3 binding came from work on tryptophan hydroxylase (6), an enzyme involved in neurotransmitter biosynthesis, and Raf, the upstream activator of the classical MAP kinase pathway (7). Work from the Shaw lab (8), building on detailed phosphorylation studies of Raf by Debbie Morrison's group, revealed that 14-3-3 proteins specifically bound to phosphoserine-containing sequences. That work, together with oriented peptide library screening on all mammalian 14-3-3 proteins by Yaffe and colleagues (9), led to the identification of two optimal phosphoserine/threonine-containing motifs – RSx[pS/pT]xP (mode-1) and Rxxx[pS/pT]xP (mode-2) – that are recognized by all 14-3-3 isotypes (9). Pro in the pS/pT+2 position is not absolutely required (9–11), and an additional motif (mode-3) has been found in proteins where the pS/pT residue is the final or next to the last residue at the C-terminus (12). Although there are clear examples of proteins and peptides that differ from these motifs, or that do not require phosphorylation at all for binding, most 14-3-3 ligands use phosphorylated sequences that closely resemble the optimal 14-3-3 consensus motifs for binding. This ability of 14-3-3 proteins to bind to large numbers of ligands in a phospho-regulated manner provides a mechanism for cytoplasmic Ser/Thr kinases, including kinases that are misregulated in cancer, such as mTor, AKT, and PKC family members, to broadly exert control over many key signaling events required for tumor cell survival.
- Type
- Chapter
- Information
- Molecular OncologyCauses of Cancer and Targets for Treatment, pp. 293 - 304Publisher: Cambridge University PressPrint publication year: 2013