CHIP: A Co-chaperone for Degradation by the Proteasome - The Networking of Chaperones by Co-chaperones - page 228

Table 11.1 (continued)

Substrate/Client Classification Disease association Reference

MAPK/ERK kinase kinase
2 (MEKK2)

Signalling
intermediate

Maruyama et al.
( 2010 )

Apoptosis signal-regulating
kinase 1 (ASK1)

Signalling
intermediate

Gao et al. ( 2010 );
Hwang et al. ( 2005 )

Leucine-rich repeat kinase
2 (LRRK2)

Signalling
intermediate

Neurodegeneration Ding and Goldberg

( 2009 ); Ko et al.
( 2009 )

Eukaryotic translation ini-
tiation factor 5A (eIF5A)

Transcription
factor

Shang et al. ( 2014 )

Estrogen Receptor (ER) Transcription

factor

Cancer Fan et al. ( 2005 )

Glucocorticoid receptor
(GR)

Transcription
factor

Wang and DeFranco
( 2005 ); Galigniana
et al. ( 2004 ); Connell
et al. ( 2001 )

Tumour protein 53 (p53) Transcription

factor

Cancer Wang et al. ( 2011 );

Sisoula et al. ( 2011 );
Muller et al. ( 2008 );
Esser et al. ( 2005 )

V-Myc Avian Myelocyto-
matosis Viral Oncogene
Homolog (c-Myc)

Transcription
factor

Cancer Paul et al. ( 2013 )

Forkhead transcription fac-
tor p (FOXp)

Transcription
factor

Chen et al. ( 2013 )

Hypoxia-inducible factor 1
alpha (HIF-1alpha)

Transcription
factor

Cancer Luo et al. ( 2010 )

Forkhead transcription fac-
tor 1 (FoxO1)

Transcription
factor

Li et al. ( 2009 )

roles in fundamental cellular processes. What is also striking is that many of
these proteins are linked with diseases including cancer and neurodegenerative
diseases like Alzheimer's disease. CHIP may therefore be of therapeutic value
given the potential ability to regulate the degradation of disease relevant proteins
like tau or p53 (Hatakeyama et al. 2004a ; Petrucelli et al. 2004 ; Shimura et al.
2004 ; Esser et al. 2005 ).
In particular, the role of CHIP in neurodegenerative diseases, where protein ag-
gregates are a hallmark, has been a main focus of research. CHIP can bind directly
to and ubiquitinate the protein tau, actions that mediate the dissolution of tau aggre-
gates (Hatakeyama et al. 2004a ; Petrucelli et al. 2004 ; Shimura et al. 2004 ). These
tau aggregates are associated with the pathology of Alzheimer's disease (Kosik
and Shimura 2005 ; Medeiros et al. 2011 ; Martin et al. 2011 ; Salminen et al. 2011 ).
CHIP may also regulate the aggregation of tau via ubiquitination of other client