Diana David, PhD Student
The highly conserved eukaryotic ubiquitin-proteasome system plays a pivotal role in protein homeostasis and is critical in regulating normal and cancer related cellular processes. The specificity and selectivity of target proteins for degradation are defined by particular E3 ubiquitin ligases. Several oncogenic E3 ubiquitin ligases have been identified as diagnostic markers or potential drug targets in human breast cancer. Smad ubiquitin regulatory factors (Smurfs) belong to the HECT- family of E3 ubiquitin ligases and comprise mainly of two members, Smurf1 and Smurf2. Initially, Smurfs have been implicated in determining the competence of cells to respond to TGF-β/BMP signalling pathway. Notably, aberrant expression of SMURF2 occurs in several types of cancers, including breast, esophageal, pancreatic and renal cell carcinomas. Nevertheless, the intrinsic catalytic activity has extended the repertoire of Smurf substrates beyond the TGF-β/BMP super family expanding its realm further to epigenetic modifications of histones governing the chromatin landscape. The present study was done to analyse the specific role of Smurf2 in regulating breast cancer cell proliferation and to identify the potential molecular targets implicated in these functions along with SMURF2.
In our study we identified a possible interaction between SMURF2 and CNKSR2 (connector enhancer of kinase suppressor of Ras 2), a scaffold protein involved in Ras signalling pathway. CNKSR2 and its homolog CNKSR1 was found to play an important role in regulating cell proliferation via the MAPK, PI3K-AKT and NF-κB pathway. Hence, studying the potential interaction between SMURF2 and CNKSR2 might pave the way to understand the role of SMURF2 in maintaining cellular homeostasis.