1gxc: Difference between revisions

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==Overview==

The Chk2 Ser/Thr kinase plays crucial, evolutionarily conserved roles in, cellular responses to DNA damage. Identification of two pro-oncogenic, mutations within the Chk2 FHA domain has highlighted its importance for, Chk2 function in checkpoint activation. The X-ray structure of the Chk2, FHA domain in complex with an in vitro selected phosphopeptide motif, reveals the determinants of binding specificity and shows that both, mutations are remote from the peptide binding site. We show that the Chk2, FHA domain mediates ATM-dependent Chk2 phosphorylation and targeting of, Chk2 to in vivo binding partners such as BRCA1 through either or both of, two structurally distinct mechanisms. Although phospho-dependent binding, is important for Chk2 activity, previously uncharacterized, phospho-independent FHA domain interactions appear to be the primary, target of oncogenic lesions.

The Chk2 Ser/Thr kinase plays crucial, evolutionarily conserved roles in cellular responses to DNA damage. Identification of two pro-oncogenic mutations within the Chk2 FHA domain has highlighted its importance for Chk2 function in checkpoint activation. The X-ray structure of the Chk2 FHA domain in complex with an in vitro selected phosphopeptide motif reveals the determinants of binding specificity and shows that both mutations are remote from the peptide binding site. We show that the Chk2 FHA domain mediates ATM-dependent Chk2 phosphorylation and targeting of Chk2 to in vivo binding partners such as BRCA1 through either or both of two structurally distinct mechanisms. Although phospho-dependent binding is important for Chk2 activity, previously uncharacterized phospho-independent FHA domain interactions appear to be the primary target of oncogenic lesions.

==Disease==

Line 18:

[[Category: Durocher, D.]]

[[Category: Goldberg, M.]]

[[Category: Haire, L.F.]]

[[Category: Haire, L F.]]

[[Category: Jackson, S.P.]]

[[Category: Jackson, S P.]]

[[Category: Li, J.]]

[[Category: Smerdon, S.J.]]

[[Category: Smerdon, S J.]]

[[Category: Wilker, E.]]

[[Category: Williams, B.L.]]

[[Category: Williams, B L.]]

[[Category: Yaffe, M.B.]]

[[Category: Yaffe, M B.]]

[[Category: checkpoint kinase]]

[[Category: phosphoprotein-binding domain]]

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[[Category: transferase]]

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@@ Line 4: / Line 4: @@
 ==Overview==
-The Chk2 Ser/Thr kinase plays crucial, evolutionarily conserved roles in, cellular responses to DNA damage. Identification of two pro-oncogenic, mutations within the Chk2 FHA domain has highlighted its importance for, Chk2 function in checkpoint activation. The X-ray structure of the Chk2, FHA domain in complex with an in vitro selected phosphopeptide motif, reveals the determinants of binding specificity and shows that both, mutations are remote from the peptide binding site. We show that the Chk2, FHA domain mediates ATM-dependent Chk2 phosphorylation and targeting of, Chk2 to in vivo binding partners such as BRCA1 through either or both of, two structurally distinct mechanisms. Although phospho-dependent binding, is important for Chk2 activity, previously uncharacterized, phospho-independent FHA domain interactions appear to be the primary, target of oncogenic lesions.
+The Chk2 Ser/Thr kinase plays crucial, evolutionarily conserved roles in cellular responses to DNA damage. Identification of two pro-oncogenic mutations within the Chk2 FHA domain has highlighted its importance for Chk2 function in checkpoint activation. The X-ray structure of the Chk2 FHA domain in complex with an in vitro selected phosphopeptide motif reveals the determinants of binding specificity and shows that both mutations are remote from the peptide binding site. We show that the Chk2 FHA domain mediates ATM-dependent Chk2 phosphorylation and targeting of Chk2 to in vivo binding partners such as BRCA1 through either or both of two structurally distinct mechanisms. Although phospho-dependent binding is important for Chk2 activity, previously uncharacterized phospho-independent FHA domain interactions appear to be the primary target of oncogenic lesions.
 ==Disease==
@@ Line 18: / Line 18: @@
 [[Category: Durocher, D.]]
 [[Category: Goldberg, M.]]
-[[Category: Haire, L.F.]]
+[[Category: Haire, L F.]]
-[[Category: Jackson, S.P.]]
+[[Category: Jackson, S P.]]
 [[Category: Li, J.]]
-[[Category: Smerdon, S.J.]]
+[[Category: Smerdon, S J.]]
 [[Category: Wilker, E.]]
-[[Category: Williams, B.L.]]
+[[Category: Williams, B L.]]
-[[Category: Yaffe, M.B.]]
+[[Category: Yaffe, M B.]]
 [[Category: checkpoint kinase]]
 [[Category: phosphoprotein-binding domain]]
@@ Line 30: / Line 30: @@
 [[Category: transferase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb  3 09:43:50 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:54:59 2008''