Actin nucleation by a transcription co-factor that links cytoskeletal events with the p53 response.
Despite its obvious importance in tumorigenesis, little information is available on the mechanisms that integrate cell motility and invasion with nuclear events.  Tumor suppressor p53 is a DNA damage responsive transcription factor which initiates a checkpoint response culminating in cell cycle arrest or apoptosis. JMY is a transcription co-factor that functions in the nucleus during the p53 response. By forming a DNA damage-dependent complex with the p300 co-activator and the Mdm2 oncoprotein, JMY takes on a significant role in regulating the p53 response.  Here, we discuss recent studies describing an unexpected cytoplasmic role of JMY in regulating cell motility and invasion.  Control of cadherin expression and actin nucleation allows JMY to influence cell motility and invasion, contrasting with its nuclear role as a p53 co-factor which drives the response to DNA damage.  JMY therefore connects cell motility and invasion with the p53 response, and its aberrant regulation is likely to significantly contribute to tumorigenesis. How these findings might relate to JMY's role as a transcription co-factor are discussed, as well as the mechanisms through which JMY integrates cytoskeletal events and cellular motility with the DNA damage response.
Coutts
Amanda S
AS
Medical Sciences Division, University of Oxford, Oxford, UK.
Weston
Louise
L
La Thangue
Nicholas B
NB
D000199:Actins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D003599:Cytoskeleton / Q000502:physiology*; D004260:DNA Repair; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017434:Protein Structure, Tertiary; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D000199:Actins; C121977:JMY protein, human; D009687:Nuclear Proteins; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53