CDCA7 (cell division control protein A7)

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Paper discussed: "The MYC-Associated Protein CDCA7 Is Phosphorylated by AKT To Regulate MYC-dependent Apoptosis and Transformation"

What is CDCA7


Cell division control protein A7 or CDCA7 is a protein often expressed in high levels in human cancers (paper specificially refers to acute myeloid leukemia, AML, and blast crisis-stage chronic myeloid leukemia, CML) and is often expressed along with high levels of MYC.

JPO2 has been discovered to have the ability to directly associate with MYC and promotes MYC dependent transformation. CDCA7 is considered to be a brother protein of JPO2 as it contains consensus sequence with JPO2 that is believe to bind to DNA (cystine rich C-terminal). The researchers of the paper wanted to determine if the CDCA7 protein can also promote MYC dependent transformation and/or have some assoication of any kind to MYC.

Regions of the CDCA7 Essential for MYC Interaction
From coprecipitation experiments and manipulating the CDCA7 gene via mutations (deletions) it was discovered the CDCA7 protein has a region that allows for interaction with MYC.

The CDCA7 region that intereacts with MYC has:


 * 1) Consensus site at threonine 163 (T163) that is shared with the AKT consenus site (RXRXX,T/S,F/L)


 * 1) NLS domain that is bi-partite


 * 1) Proline residue facilitating the binding of 14-3-3 protein

These 3 regions in the CDCA7 were tested in experiments described in the paper to determine their role in how CDCA7 interacts with MYC and to determine whether CDCA7 plays a role in MYC activity

Modes of Interactions between CDCA7 and MYC
1) Phosphorylation


 * The T163 site of CDCA7 was determined to be a phosphorlyation site from phospotryptic mapping (maps parts of protein that can specificially be phosphorlyated) and through anti-bodies designed to bind to phosphorlyated T163 CDCA7, because sharing a consenus site with AKT does not necessarily mean phosphorlyation occurs at T163 of CDCA7. Further evidence was gathered that T163 of CDCA7 is a phosphorlyation site in that when T163 was mutated so that Theroine (T) was switched to be an Alanine (A) the α-P-T163 (the anti-body) reacted wtih the wild-type (T163) and not with the mutant (T163A).


 * With the confirmation that T163 of CDCA7 is a phosphorlyation site, the experimenters went on to test if the AKT protein phosphorylates T163 of CDCA7. Through inhibiting AKT, the phosphorlyation of CDCA7 decreases and when using the T163A mutants the AKT were unable to phosphorlyate CDCA7.