tumour suppressor protein PTEN in vitro, resulting in PTEN proteasomal degradation or trafficking. The in vivo role of NEDD4 in PTEN regulation is less clear. There is some evidence from NEDD4 deficient mice that NEDD4 does not target PTEN for degradation or trafficking. However, in other in vivo models, and in many human cancer cell lines, NEDD4 does appear responsible for the degradation of PTEN. NEDD4 regulation of PTEN may only occur in specific biological contexts. The role of NEDD4 in negatively regulating tumour suppressor proteins is consistent with the frequent overexpression of NEDD4 in many different types of human cancers. Decreased levels of NEDD4 have also been associated with some cancers, including neuroblastoma and pancreatic cancer where the NEDD4 directly targets the respective oncoproteins N-Myc and c-Myc associated with these cancers for degradation. Viral budding NEDD4 may be hijacked by viral proteins (for example, by UL56 from Herpes simplex virus 2, or by protein VP40 from Ebola virus. Such infection aids viruses in taking over the ESCRT pathway which is essential for successful budding of the virions from the plasma membrane. The hijacking mechanisms operate by exploiting evolution, the chemical evolution of (viral) genes coding for traits that exploit a short linear motif mimicry. In the case of NEDD4, viral proteins mimic the PPxY recognition motif of WW domains that are part of NEDD4. Notes References External links Human proteins