Figure 1. Role of ERK8 in maintaining... | Rockefeller University Press

Figure 1.

$Figure 1. Role of ERK8 in maintaining genome stability. (A) In normal cells, chromatin-bound ERK8 interacts with the chromatin fraction of PCNA, which resides at the replication fork (here just shown at the leading strand for simplicity). ERK8 binding inhibits the E3 ubiquitin ligase HDM2 from interacting with PCNA. (B) In cancer cells, inactivation of ERK8 enables HDM2 to interact with and ubiquitinate PCNA, targeting it for degradation. A decrease in PCNA levels causes an increase in DNA damage, resulting in the accumulation of new mutations. These new mutations may render HDM2 nonfunctional (rectangular form), which ultimately results in an increase of PCNA stability and facilitates cell proliferation. The homotrimeric PCNA structure (Protein Data Bank ID 2OD8) was generated using the Chimera software program (Pettersen et al., 2004).$

Role of ERK8 in maintaining genome stability. (A) In normal cells, chromatin-bound ERK8 interacts with the chromatin fraction of PCNA, which resides at the replication fork (here just shown at the leading strand for simplicity). ERK8 binding inhibits the E3 ubiquitin ligase HDM2 from interacting with PCNA. (B) In cancer cells, inactivation of ERK8 enables HDM2 to interact with and ubiquitinate PCNA, targeting it for degradation. A decrease in PCNA levels causes an increase in DNA damage, resulting in the accumulation of new mutations. These new mutations may render HDM2 nonfunctional (rectangular form), which ultimately results in an increase of PCNA stability and facilitates cell proliferation. The homotrimeric PCNA structure (Protein Data Bank ID 2OD8) was generated using the Chimera software program (Pettersen et al., 2004).

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