Download Moonlighting and pleiotropy among regulators of the degradation

P008
Moonlighting and pleiotropy among regulators of the
degradation machinery
Elah Pick1 and Giovanna Serino2
1
University of Haifa, Oranim Campus, Tivon, Israel
2
Sapienza Università di Roma, Roma, Italy
Multifunctional proteins are generally referred to as either pleiotropic or moonlighting proteins. Although define similarly, the
meaning is these terms is quite different. While a moonlighting
protein harbors several autonomous functions, pleiotropy refers
to a single-functional protein, which influences –through a similar
mechanism– the activity of downstream proteins involved in
distinct cellular pathways. These features are hard to discriminate, especially in orphan proteins that carry out alone several
functions. However, multisubunit enzymes can be good model
since a mutation in single subunit might cause to both complexdependent and unique (complex-independent), phenotypes/
activities. We will discuss recent results on two paralog regulators
of the protein degradation machinery, the proteasome lid and the
CSN complexes, which exhibit both moonlighting and pleiotropic
features. Each of the two complexes is involved in a distinct
cellular activity: the CSN promotes the function of a large family
of ubiquitin E3 ligases known as CRLs, while the proteasome
lid is required for ubiquitin hydrolysis from proteasome
substrates before degradation. Both complexes determine the
fate of hundreds of proteins, and therefore, malfunctioning of
each, causes the failure of many cellular processes. However,
a single-subunit mutation in each complex leads both to a
common phenotype related with the complex activity,and unique
phenotypes. Different unique features seem to be a hallmark of
specific subunits of these complexes and our studies suggest that
they have been broadly adopted across phyla.