Control of cell cycle exit and neuronal differentiation by SCF and APC/C ubiquitin ligases
Author(s)
Guardavaccaro, Daniele
Date Issued
April 12, 2012
Type
Doctoral Thesis
Abstract
We have developed several assays based on immunopurification strategies
followed by mass spectrometry analysis to systematically identify novel
substrates of APC/C and SCF ubiquitin ligases. Using these assays we have
identified a number of novel substrates of the SCFβTrCP and the APC/CCdh1
ubiquitin ligases. We have made the decision to focus on three transcriptional
regulators, namely TFAP4, targeted for degradation by SCFβTrCP, and E2F3 and
E2F6, targeted for degradation by APC/CCdh1. We have found that proteasomedependent
degradation of these three transcriptional regulators occurs during cell
cycle exit and neuronal differentiation. The major aims of this work are to
biochemically characterize the proteasome-dependent degradation of TFAP4,
mediated by SCFβTrCP, and the ones of E2F3 and E2F6, mediated by APC/CCdh1,
and to investigate the biological function of their degradation during cell cycle exit
and neuronal differentiation.
Additional information
Dottorato in Genetica e biologia molecolare
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