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THE EYA
PHOSPHATASE
Its unique role in cancer
2018-02-15 K.Guna Pragna 16BCE0942 1
What is Eya protein??
• The Eya proteins were originally identified as essential transcriptional co-
activators of the Six family of homeoproteins.
• Eya proteins were first identified as essential co-activators of the Six family of
homeoproteins, which are expressed during early embryogenesis and essential for
the development of numerous organs
• Given below is the representation of the eya protein.
2018-02-15 K. Guna Pragna 16BCE0942 2
2018-02-15 K.Guna Pragna 16BCE0942 3
Composition of Eya protein
• Subsequently, the highly conserved C-terminal domains of the Eya proteins were
discovered to act as a Mg2+-dependentTyr phosphatases, making Eyas the
first transcriptional activators to harbor intrinsic phosphatase activity
2018-02-15 K.Guna Pragna 16BCE0942 4
Eya protein in Cancer cells
• Only two direct targets of the EyaTyr phosphatase have been identified: H2AX,
whose dephosphorylation directs cells to the DNA repair instead of the apoptotic
pathway upon DNA damage, and ERβ, whose dephosphorylation inhibits its anti-
tumor transcriptional activity.
• The EyaTyr phosphatase mediates breast cancer cell transformation, migration,
invasion, as well as metastasis, through targets not yet identified.
2018-02-15 K.Guna Pragna 16BCE0942 5
2018-02-15 K.Guna Pragna 16BCE0942 6
Why the Eya protein is used in the cancer
cells??
• Intriguingly, the N-terminal domain of Eya contains a separate Ser/Thr
phosphatase activity implicated in innate immunity and in regulating c-
Myc stability.
• Thus, Eya proteins are highly complex, containing two separable phosphatase
domains and a transcriptional activation domain, thereby influencing tumor
progression through multiple mechanisms.
• The many functions of the phosphatase activities of Eya proteins using the 526
amino acid-mEya3 is given below
2018-02-15 K.Guna Pragna 16BCE0942 7
2018-02-15 K.Guna Pragna 16BCE0942 8
Steps to cure cancer by Eya protein….
1) TheTyr phosphatase activity of Eya
2) Eya’s Ser/Thr phosphatase activity
3) Targeting the Eya phosphatase for potential cancer therapy
2018-02-15 K.Guna Pragna 16BCE0942 9
Mechanism of Eya Protien…
• Eya proteins are critical for the development of multiple organs, in part by acting
with Six proteins to promote proliferation and survival of progenitor
cell populations. Mutations in Six1 and Eyas lead to various genetic disorders.The
crystal structure of maltose binding protein fused Six1 in complex with Eya2 ED
has been determined, revealing the molecular details of the Eya2 ED-Six1
interaction, as well as the structural basis of mutations causing branchio-oto-renal
syndrome.
• Six and Eya family members are typically down regulated after organ
development is complete, but various Six and Eya family members are re-
expressed in multiple tumor types, including ovarian breast Overexpression of
either Six1 or Eya correlates with recurrence, metastasis, and decreased overall
survival in a variety of tumor types.
2018-02-15 K.Guna Pragna 16BCE0942 10
2018-02-15 K.Guna Pragna 16BCE0942 11

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Eya phosphate - the cancer prevention role

  • 1. THE EYA PHOSPHATASE Its unique role in cancer 2018-02-15 K.Guna Pragna 16BCE0942 1
  • 2. What is Eya protein?? • The Eya proteins were originally identified as essential transcriptional co- activators of the Six family of homeoproteins. • Eya proteins were first identified as essential co-activators of the Six family of homeoproteins, which are expressed during early embryogenesis and essential for the development of numerous organs • Given below is the representation of the eya protein. 2018-02-15 K. Guna Pragna 16BCE0942 2
  • 4. Composition of Eya protein • Subsequently, the highly conserved C-terminal domains of the Eya proteins were discovered to act as a Mg2+-dependentTyr phosphatases, making Eyas the first transcriptional activators to harbor intrinsic phosphatase activity 2018-02-15 K.Guna Pragna 16BCE0942 4
  • 5. Eya protein in Cancer cells • Only two direct targets of the EyaTyr phosphatase have been identified: H2AX, whose dephosphorylation directs cells to the DNA repair instead of the apoptotic pathway upon DNA damage, and ERβ, whose dephosphorylation inhibits its anti- tumor transcriptional activity. • The EyaTyr phosphatase mediates breast cancer cell transformation, migration, invasion, as well as metastasis, through targets not yet identified. 2018-02-15 K.Guna Pragna 16BCE0942 5
  • 7. Why the Eya protein is used in the cancer cells?? • Intriguingly, the N-terminal domain of Eya contains a separate Ser/Thr phosphatase activity implicated in innate immunity and in regulating c- Myc stability. • Thus, Eya proteins are highly complex, containing two separable phosphatase domains and a transcriptional activation domain, thereby influencing tumor progression through multiple mechanisms. • The many functions of the phosphatase activities of Eya proteins using the 526 amino acid-mEya3 is given below 2018-02-15 K.Guna Pragna 16BCE0942 7
  • 9. Steps to cure cancer by Eya protein…. 1) TheTyr phosphatase activity of Eya 2) Eya’s Ser/Thr phosphatase activity 3) Targeting the Eya phosphatase for potential cancer therapy 2018-02-15 K.Guna Pragna 16BCE0942 9
  • 10. Mechanism of Eya Protien… • Eya proteins are critical for the development of multiple organs, in part by acting with Six proteins to promote proliferation and survival of progenitor cell populations. Mutations in Six1 and Eyas lead to various genetic disorders.The crystal structure of maltose binding protein fused Six1 in complex with Eya2 ED has been determined, revealing the molecular details of the Eya2 ED-Six1 interaction, as well as the structural basis of mutations causing branchio-oto-renal syndrome. • Six and Eya family members are typically down regulated after organ development is complete, but various Six and Eya family members are re- expressed in multiple tumor types, including ovarian breast Overexpression of either Six1 or Eya correlates with recurrence, metastasis, and decreased overall survival in a variety of tumor types. 2018-02-15 K.Guna Pragna 16BCE0942 10
  • 11. 2018-02-15 K.Guna Pragna 16BCE0942 11