C-terminus of Hsc70-interacting protein regulates C-terminal binding protein 2 and the expression of its target genes

Lee, Ji Sun; Yoo, Soon Ji

doi:10.1016/j.bbrc.2013.01.124

Cited by 11 publications

(6 citation statements)

References 31 publications

(53 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hsp90 client protein, migration inhibitory factor (MIF), which is involved in many signaling pathways, is also a well-known substrate of CHIP (Schulz et al, 2012 ). Breakpoint cluster abelson murine leukemia viral oncogene (BCR-ABL) and C-terminal binding protein 2 (CtBP2) are other two proteins, added in this list of CHIP substrates (Tsukahara and Maru, 2010 ; Lee and Yoo, 2013 ).…”

Section: Chip: a Quality Controller Of Cellular Proteomementioning

confidence: 99%

A Decade of Boon or Burden: What Has the CHIP Ever Done for Cellular Protein Quality Control Mechanism Implicated in Neurodegeneration and Aging?

Joshi

Amanullah

Upadhyay

et al. 2016

Front. Mol. Neurosci.

View full text Add to dashboard Cite

Cells regularly synthesize new proteins to replace old and abnormal proteins for normal cellular functions. Two significant protein quality control pathways inside the cellular milieu are ubiquitin proteasome system (UPS) and autophagy. Autophagy is known for bulk clearance of cytoplasmic aggregated proteins, whereas the specificity of protein degradation by UPS comes from E3 ubiquitin ligases. Few E3 ubiquitin ligases, like C-terminus of Hsc70-interacting protein (CHIP) not only take part in protein quality control pathways, but also plays a key regulatory role in other cellular processes like signaling, development, DNA damage repair, immunity and aging. CHIP targets misfolded proteins for their degradation through proteasome, as well as autophagy; simultaneously, with the help of chaperones, it also regulates folding attempts for misfolded proteins. The broad range of CHIP substrates and their associations with multiple pathologies make it a key molecule to work upon and focus for future therapeutic interventions. E3 ubiquitin ligase CHIP interacts and degrades many protein inclusions formed in neurodegenerative diseases. The presence of CHIP at various nodes of cellular protein-protein interaction network presents this molecule as a potential candidate for further research. In this review, we have explored a wide range of functionality of CHIP inside cells by a detailed presentation of its co-chaperone, E3 and E4 enzyme like functions, with central focus on its protein quality control roles in neurodegenerative diseases. We have also raised many unexplored but expected fundamental questions regarding CHIP functions, which generate hopes for its future applications in research, as well as drug discovery.

show abstract

Section: Chip: a Quality Controller Of Cellular Proteomementioning

confidence: 99%

A Decade of Boon or Burden: What Has the CHIP Ever Done for Cellular Protein Quality Control Mechanism Implicated in Neurodegeneration and Aging?

Joshi

Amanullah

Upadhyay

et al. 2016

Front. Mol. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Though the mechanism of degradation has yet to be fully described, the removal of phosphorylated CtBP from promoter bound locations is thought to require the action of the transducin beta family of chaperone-like molecules, TBL1 [67]. Finally, very recently the C-terminus of Hsc70-interacting protein was found to interact with CtBP2 leading to its ubiquitination and subsequent degradation in the proteasome [95]. …”

Section: Posttranslational Regulation Of Ctbpmentioning

confidence: 99%

C-Terminal Binding Protein: A Molecular Link between Metabolic Imbalance and Epigenetic Regulation in Breast Cancer

Byun

Gardner

2013

International Journal of Cell Biology

View full text Add to dashboard Cite

The prevalence of obesity has given rise to significant global concerns as numerous population-based studies demonstrate an incontrovertible association between obesity and breast cancer. Mechanisms proposed to account for this linkage include exaggerated levels of carbohydrate substrates, elevated levels of circulating mitogenic hormones, and inflammatory cytokines that impinge on epithelial programming in many tissues. Moreover, recently many scientists have rediscovered the observation, first described by Otto Warburg nearly a century ago, that most cancer cells undergo a dramatic metabolic shift in energy utilization and expenditure that fuels and supports the cellular expansion associated with malignant proliferation. This shift in substrate oxidation comes at the cost of sharp changes in the levels of the high energy intermediate, nicotinamide adenine dinucleotide (NADH). In this review, we discuss a novel example of how shifts in the concentration and flux of substrates metabolized and generated during carbohydrate metabolism represent components of a signaling network that can influence epigenetic regulatory events in the nucleus. We refer to this regulatory process as “metabolic transduction” and describe how the C-terminal binding protein (CtBP) family of NADH-dependent nuclear regulators represents a primary example of how cellular metabolic status can influence epigenetic control of cellular function and fate.

show abstract

“…In breast cancer, the oncogene effects of CHIP were reported by regulating PTEN and Pfn1 (15,20,21). However, the tumor suppressor effects of CHIP were reported by targeting TRAF2, ErbB2, ERα, MIF, PTK6, SRC-3, CtBP2 (7,(22)(23)(24)(25)(26)(27)(28)(29). However, in prostate cancer, CHIP was reported as an oncogene by targeting PTEN and Mst1, and as a tumor suppressor by targeting AR (16,19,30).…”

Section: Discussionmentioning

confidence: 99%

Carboxy-terminus Hsc70 interacting protein exerts a tumor inhibition function in head and neck cancer

et al. 2017

View full text Add to dashboard Cite

Several independent studies have reported the roles of the E3 ubiquitin ligase, carboxy-terminus Hsc70 interacting protein (CHIP) in various types of cancers. However, the biological effects of CHIP vary in regards to different cancers, and the role of CHIP in head and neck cancers (HNCs) remains unknown. In the present study, CHIP overexpression plasmids and CHIP knockdown lentivirus were constructed to affect the expression levels of CHIP protein and biological behaviors in HNC cell lines bilaterally. The biological behaviors regulated by CHIP in HNCs were investigated both in vivo and in vitro with a series of assays and analyses. A tissue microarray was stained and analyzed for the clinical significance of CHIP expression in HNCs. We identified that CHIP suppressed the malignant behaviors of HNCs in a series of in vitro and in vivo experiments, but not its two loss-of-function mutants. However, we observed an altered expression pattern of CHIP from a well, moderate, to poor differentiation pathological status in HNC specimens. In a retrospective cohort of HNCs, lower expression of CHIP indicated a poor differentiation status in tumors and a lower overall survival rate. The present study demonstrated that CHIP functions as a tumor suppressor in HNCs. In conclusion, we demonstrated that suppressed expression of CHIP may result in the progression of HNCs.

show abstract

C-terminus of Hsc70-interacting protein regulates C-terminal binding protein 2 and the expression of its target genes

Cited by 11 publications

References 31 publications

A Decade of Boon or Burden: What Has the CHIP Ever Done for Cellular Protein Quality Control Mechanism Implicated in Neurodegeneration and Aging?

A Decade of Boon or Burden: What Has the CHIP Ever Done for Cellular Protein Quality Control Mechanism Implicated in Neurodegeneration and Aging?

C-Terminal Binding Protein: A Molecular Link between Metabolic Imbalance and Epigenetic Regulation in Breast Cancer

Carboxy-terminus Hsc70 interacting protein exerts a tumor inhibition function in head and neck cancer

Contact Info

Product

Resources

About