p23 and Aha1 - The Networking of Chaperones by Co-chaperones - page 119

to play a protective role during apoptosis (Pandey et al. 2000 ; Lanneau et al. 2007 ).
The fact that p23's chaperone function has evolved as a point of attack demonstrates
the importance of this protein.
Nuclear Functions of p23
As mentioned before, p23 is not only localized in the nucleus but also shows a
bias for nuclear processes (Freeman et al. 2000 ; Echtenkamp et al. 2011 ). p23 was
found to play a role in telomere maintenance (Toogun et al. 2007 ), DNA repair
(Echtenkamp et al. 2011 ) and transcription processes (Zelin et al. 2012 ). Even
though Hsp90 and p23 have long been known to be involved in altering telomerase
activity (Holt et al. 1999 ), the actions of both chaperones are independent and op-
posed. While Hsp90 promotes the assembly of the DNA-telomerase complex, p23
fosters its disassembly (Toogun et al. 2008 ). Furthermore, this function relies on its
chaperoning activity (Toogun et al. 2007 ).
p23 also initiates the disassembly of various other protein-DNA complexes and
teams up with the acetyltransferase GCN5 to regulate transcriptional activities in re-
sponse to cellular signals (Zelin et al. 2012 ). In this recently discovered function of
p23, GCN5 acetylates the released protein after the p23-induced disassembly of the
protein-DNA complex. To control GCN5 action and re-assembly, p23 interacts with
GCN5. Only the continuing existence of the transcription activating signal removes
both the GCN5 and the inhibiting acetyl moiety to allow re-assembly of the protein
to the DNA (Zelin et al. 2012 ).
By destabilizing various protein-DNA complexes in the nucleus, p23 provides
the possibility to stop signaling and re-assemble protein-DNA complexes in re-
sponse to new internal and external stimuli. Hence, p23 contributes to a dynam-
ic signaling-response environment in the nucleus. Since the nuclear functions of
p23 have only been recently addressed, future investigations may unravel further
functions of p23 in this context.
The Cochaperone Aha1
Discovery and Occurrence
Compared to the discovery date of p23, Aha1 is a relative young cochaperone of
Hsp90, as it was first described in this context in 2002 (Panaretou et al. 2002 ).
One year earlier it was identified as a 38-kDa protein (p38) interacting with the
vesicular stomatitis virus glycoprotein (VSV-G) and modulating its transit from
the ER to the Golgi apparatus (Sevier and Machamer 2001 ). Due to its prominent
function as an a ctivator of the H sp90 A TPase, the name Aha1 prevailed. Its iden-
tification as an Hsp90 cochaperone was based on a homology search of Hch1.
This protein has been previously described as a “ h igh c opy suppressor of H sp90