14.3.3 Proteins

14.3.3 proteins are a group of highly conserved proteins that are involved in many vital cellular processes such as metabolism, protein trafficking, signal transduction, apoptosis and cell cycle regulation. 14.3.3 proteins are phospho-serine/-threonine binding proteins.

Products
Background
Literature
Pathways
Gene Data

Inhibitors

Cat No Product Name / Activity
2145 Difopein
High affinity inhibitor of 14.3.3 proteins; induces apoptosis
2144 R18
Inhibitor of 14.3.3 proteins

Related Targets

14.3.3 proteins are a group of highly conserved proteins that are involved in many vital cellular processes such as metabolism, protein trafficking, signal transduction, apoptosis and cell cycle regulation. 14.3.3 proteins are phospho-serine/-threonine binding proteins that have a diverse array of partners including transcription factors, biosynthetic enzymes, cytoskeletal proteins, signaling molecules, apoptosis factors and tumor suppressors.

The 14.3.3 family consists of 7 isoforms; β, γ, ε, σ, ζ, τ and η. 14.3.3 proteins are ubiquitously expressed and self assemble into homo- and heterodimers, with the exception of 14.3.3σ, which exclusively forms homodimers and is found in cells of epithelial origin only. Each monomer contains an independent ligand-binding site, thus the 14.3.3 dimer can interact with two target proteins simultaneously. 14.3.3 proteins are highly rigid structures and ligand binding can induce conformational changes that alter the stability and/or catalytic activity of the ligand. Furthermore, 14.3.3 protein binding can physically occlude sequence-specific or structural motifs on the target that prevent molecular interactions and/or modulate the accessibility of a target protein to modifying enzymes such as kinases, Phosphatases and proteases. In addition, 14.3.3 proteins can act as a scaffold molecule to anchor target proteins within close proximity of one another.

14.3.3 proteins are regulated by post-translational modifications such as phosphorylation, and by the binding of cofactors. Phosphorylation sites on 14.3.3 proteins are not conserved between family members and thus enable selective isoform regulation.

14.3.3 proteins represent an integration point for proliferative, survival, apoptotic and stress signaling pathways. Members of the 14.3.3 protein family enhance the activity of many proteins with proliferative and/or survival functions, such as Raf kinases, and antagonize the activity of proteins that promote cell death and senescence, such as Bad, Bim and Bax. In contrast, 14.3.3σ acts as a tumor suppressor and its expression is upregulated coordinately with p53 and BRAC1. This isoform sequesters cdk1-cyclin B complexes in the cytoplasm, and thus delays cell cycle progression. 14.3.3σ is also a crucial regulator of translation during mitosis.

Because many 14.3.3 interactions are phosphorylation dependent, 14.3.3 proteins have been integrated into the core regulatory pathways that are crucial for normal growth and development. 14.3.3 proteins are directly involved in cellular processes such as cytokinesis, cell-contact inhibition, anchorage-independent growth and cell adhesion, and it is these pathways that often become dysregulated in disease states such as cancer. Recent research has also demonstrated an involvement of 14.3.3 proteins as "reader" domains of epigenetic marks.

Literature for 14.3.3 Proteins

Cancer

Cancer Research Product Guide

A collection of over 750 products for cancer research, the guide includes research tools for the study of:

  • Cancer Metabolism
  • Epigenetics in Cancer
  • Receptor Signaling
  • Cell Cycle and DNA Damage Repair
  • Angiogenesis
  • Invasion and Metastasis
Cell Cycle & DNA Damage Repair

Cell Cycle & DNA Damage Repair Poster

In normal cells, each stage of the cell cycle is tightly regulated, however in cancer cells many genes and proteins that are involved in the regulation of the cell cycle are mutated or over expressed. Adapted from the 2015 Cancer Product Guide, Edition 3, this poster summarizes the stages of the cell cycle and DNA repair. It also highlights strategies for enhancing replicative stress in cancer cells to force mitotic catastrophe and cell death.

Programmed Cell Death

Programmed Cell Death Poster

There are two currently recognized forms of programmed cell death: apoptosis and necroptosis. This poster summarizes the signaling pathways involved in apoptosis, necroptosis and cell survival following death receptor activation, and highlights the influence of the molecular switch, cFLIP, on cell fate.

Pathways for 14.3.3 Proteins

Apoptosis

Apoptosis Signaling Pathway

Apoptosis is a physiological process for cell death that is critical during aging and development. It may also be referred to as cell 'suicide'. Apoptosis can be triggered by events both inside and outside of the cell.

14-3-3 Gene Data

Gene Species Gene Symbol Gene Accession No. Protein Accession No.
14-3-3β Human YWHAB NM_003404 P31946
Mouse Ywhab NM_018753 Q9CQV8
Rat Ywhab NM_019377 P35213
14-3-3ε Human YWHAE NM_006761 P62258
Mouse Ywhae NM_009536 P62259
Rat Ywhae NM_031603 P62260
14-3-3γ Human YWHAG NM_012479 P61981
Mouse Ywhag NM_018871 P61982
Rat Ywhag NM_019376 P61983
14-3-3η Human YWHAH NM_003405 Q04917
Mouse Ywhah NM_011738 P68510
Rat Ywhah NM_013052 P68511
14-3-3τ Human YWHAQ NM_006826 P27348
Mouse Ywhaq NM_011739 P68254
Rat Ywhaq NM_013053 P68255
14-3-3ζ Human YWHAZ NM_145690 Q6P3U9
Mouse Ywhaz NM_011740 P63101
Rat Ywhaz NM_013011 P63102
14-3-3σ
(Stratifin)
Human YWHAS NM_006142 P31947
Mouse Ywhas NM_018754 O70456
Rat - - -