[6][7] 14-3-3ζ is a major regulator of apoptotic pathways critical to cell survival and plays a key role in a number of cancers and neurodegenerative diseases.

[8][9][11][12][15] This combination of dependence on phosphorylation and widespread biological impact results in dynamic regulation of multiple signalling pathways and allows for cellular adaptation to environmental changes.

[8] In particular, 14-3-3ζ is a key player in regulating cell survival and interacts with many apoptotic proteins, including Raf kinases, BAX, BAD, NOXA, and caspase-2.

[9] As a result, 14-3-3ζ functions to protect the cell from environmental stresses, such as chemotherapy-induced death, anoikis, growth factor deprivation, and hypoxia.

For instance, 14-3-3ζ controls cellular senescence by complexing with BIS to chaperone protein folding of STAT3 and activate the signaling pathway.

[12] Its localization to both the cytoplasm and nucleus also suggests a role in gene expression, possibly through regulation of transcription factor activity.

[9] Emerging literature shows the increased presence of the anti-14-3-3ζ antibodies in several immune dysfunctions, including human vasculitis and cancer.

In later stages of apoptosis the entire cell becomes fragmented, forming a number of plasma membrane-bounded apoptotic bodies which contain nuclear and or cytoplasmic elements.

The ultrastructural appearance of necrosis is quite different, the main features being mitochondrial swelling, plasma membrane breakdown and cellular disintegration.

[25][26] Furthermore, recent studies have shown the 14-3-3ζ plays a significant clinical role in the suppression of the RA symptoms in experimental animals.

A significantly greater bone loss and immune cell infiltration in the synovial joints was observed in the arthritic 14-3-3ζ KO animals.