ARF-Like (ARL) Proteins - Ras Superfamily Small G Proteins: Biology and Mechanisms 2 - page 235

domain, and this has been shown to be involved in establishment of the replicative
organelle (Nagai et al. 2002 ; Amor et al. 2005 ; Alix et al. 2012 ). Thus the ARLs and
their interaction partners have already proven to be a rich source of proteins
implicated in human diseases and therefore a clinically important group of cell
signalers. The fact that several members of the family are ancient regulators of
essential cell functions has made them targets for use by opportunistic pathogens
that exploit such pathways and mutations in nonessential GTPases or their modu-
lators can impair the normally highly regulated signals into ones more conducive to
human pathologies. The facts that ARLs typically perform multiple functions in all
cells and that protein-protein interactions are challenging drug targets might
dampen enthusiasm for pursuit of ARLs as chemotherapeutic targets. The utility
of drugs like Brefeldin A (Misumi et al. 1986 ; Ishii et al. 1989 ; Sausville et al. 1996 )
and Golgicide A (Saenz et al. 2009 ) in the research setting offer cause for real
optimism that drugs of enormous value in the clinic may be within sight (Viaud
et al. 2007 ; Vigil et al. 2010 ). But for now there are many, many important and
unanswered questions to be addressed about the roles and mechanisms of this
important family of cell regulators of basic cell function and their links to human
diseases.
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