Ubiquitin-conjugating partners of CHIP:
In section 3, after " fate of substrates":
E2’s are the family of enzymes, having highly conserved ubiquitin conjugating domains. These enzymes, in combination with E3s, play an important role in determining the fate of substrate proteins by selecting a lysine residue on which ubiquitin moiety must be added.
In section 3, after Murata, et al. 2003:
An in vitro study has shown that CHIP, with the aid of UbcH5 and UbcH6, two other E2s, can efficiently ubiquitinate interferon regulatory factor (IRF1) giving an idea of its modulation, under stress conditions (Narayan et al., 2011). Similarly, another study based on CHIP U-box domain showed that eight E2’s (Ube2D1, Ube2D2, Ube2D3, Ube2E1, Ube2E2, Ube2E3, …show more content…
The study conducted by Yang et al. shows that CHIP regulates the level of katanin-p60 protein, which is required for the proper axonal growth in early developmental stages. CHIP antagonizes the effects of a deubiquitylating enzyme, USP47 by ubiquitinating and destabilizing katanin-p60 and hence presents an important role in axonal growth (Yang et al., 2013). Another study showed abnormal motor disturbances with altered phenotypic and behavioral functions in CHIP heterozygous mice (McLaughlin et al., 2012). CHIP may also have some indirect regulatory roles over various neurodevelopmental processes through its large number of substrates, where it regulates various proteins which are directly involved in brain development processes. For example, one of its substrates, PTEN is a key signaling molecule having direct roles in various developmental processes like neuronal differentiation and neurite growth (Li et al., 2003;Hsia et al., 2014). The cellular level of PTEN is largely regulated by its proteasomal degradation, which is governed by E3 ubiquitin ligases including CHIP (Ahmed et al., 2012). Cytoskeleton of large neurons and axons are majorly built by cytoskeletal proteins, neurofilaments. Evidence shows that CHIP has a direct involvement in proteasomal degradation of neurofilaments medium subunit of 95kDa, which are highly damaged and decreased in the less understood …show more content…
CHIP linked substrates in multiple cellular pathways and abnormalities: CHIP substrates form a large group of proteins, implicated in various important pathways and pathologies. Substrates are subdivided in accordance with their association with cancer, neurodegeneration, signaling, transcriptional regulation, and development. Substrates have been put into different boxes according to their degradative pathways. Yellow boxes represent substrates, which are degraded by the proteasome, whereas brown boxes represent the lysosomal degradation of CHIP substrates. Substrates degraded by both proteasomal and lysosomal pathways are shown in the green box. CHIP also ubiquitinates few of its substrates to functionally regulate them instead of degrading, shown within the purple
In section 3, after " fate of substrates":
E2’s are the family of enzymes, having highly conserved ubiquitin conjugating domains. These enzymes, in combination with E3s, play an important role in determining the fate of substrate proteins by selecting a lysine residue on which ubiquitin moiety must be added.
In section 3, after Murata, et al. 2003:
An in vitro study has shown that CHIP, with the aid of UbcH5 and UbcH6, two other E2s, can efficiently ubiquitinate interferon regulatory factor (IRF1) giving an idea of its modulation, under stress conditions (Narayan et al., 2011). Similarly, another study based on CHIP U-box domain showed that eight E2’s (Ube2D1, Ube2D2, Ube2D3, Ube2E1, Ube2E2, Ube2E3, …show more content…
The study conducted by Yang et al. shows that CHIP regulates the level of katanin-p60 protein, which is required for the proper axonal growth in early developmental stages. CHIP antagonizes the effects of a deubiquitylating enzyme, USP47 by ubiquitinating and destabilizing katanin-p60 and hence presents an important role in axonal growth (Yang et al., 2013). Another study showed abnormal motor disturbances with altered phenotypic and behavioral functions in CHIP heterozygous mice (McLaughlin et al., 2012). CHIP may also have some indirect regulatory roles over various neurodevelopmental processes through its large number of substrates, where it regulates various proteins which are directly involved in brain development processes. For example, one of its substrates, PTEN is a key signaling molecule having direct roles in various developmental processes like neuronal differentiation and neurite growth (Li et al., 2003;Hsia et al., 2014). The cellular level of PTEN is largely regulated by its proteasomal degradation, which is governed by E3 ubiquitin ligases including CHIP (Ahmed et al., 2012). Cytoskeleton of large neurons and axons are majorly built by cytoskeletal proteins, neurofilaments. Evidence shows that CHIP has a direct involvement in proteasomal degradation of neurofilaments medium subunit of 95kDa, which are highly damaged and decreased in the less understood …show more content…
CHIP linked substrates in multiple cellular pathways and abnormalities: CHIP substrates form a large group of proteins, implicated in various important pathways and pathologies. Substrates are subdivided in accordance with their association with cancer, neurodegeneration, signaling, transcriptional regulation, and development. Substrates have been put into different boxes according to their degradative pathways. Yellow boxes represent substrates, which are degraded by the proteasome, whereas brown boxes represent the lysosomal degradation of CHIP substrates. Substrates degraded by both proteasomal and lysosomal pathways are shown in the green box. CHIP also ubiquitinates few of its substrates to functionally regulate them instead of degrading, shown within the purple