C-terminus of Hsc70-interacting protein regulates profilin1 and breast cancer cell migration

Choi, Ye Na; Lee, Sun Kyung; Seo, Tae Woong; Lee, Ji Sun; Yoo, Soon Ji

doi:10.1016/j.bbrc.2014.03.061

Cited by 29 publications

(24 citation statements)

References 34 publications

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“…Although increasing evidence has indicated that CHIP plays an important role in cancers [ 6 , 28 – 30 ], the mechanisms of CHIP regulation remained poorly understood. Up to now, there were only two published studies focused on the mechanisms of upstream regulation of CHIP.…”

Section: Discussionmentioning

confidence: 99%

MiR-1178 Promotes the Proliferation, G1/S Transition, Migration and Invasion of Pancreatic Cancer Cells by Targeting CHIP

Cao

Huang

et al. 2015

PLoS ONE

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CHIP, a co-chaperone protein that interacts with Hsc/Hsp70, has been shown to be under-expressed in pancreatic cancer cells and has demonstrated a potential tumor suppressor property. Nevertheless, the underlying mechanisms of CHIP regulation in pancreatic cancer cells remain unknown. In this study, we found that miR-1178 decreased the translation of the CHIP protein by targeting the 3′-UTR region. We observed that over-expression of miR-1178 facilitated the proliferation, G1/S transition, migration and invasion of pancreatic cancer cells. Conversely, the inhibition of miR-1178 expression significantly suppressed these phenotypes. Furthermore, CHIP over-expression abrogated miR-1178-induced cell proliferation and invasion. Our data suggest that miR-1178 acts as an oncomiR in pancreatic cancer cells by inhibiting CHIP expression.

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Section: Discussionmentioning

confidence: 99%

MiR-1178 Promotes the Proliferation, G1/S Transition, Migration and Invasion of Pancreatic Cancer Cells by Targeting CHIP

Cao

Huang

et al. 2015

PLoS ONE

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“…Choi et al [70] showed in 2014 that profilin1 interacts with C-terminus of Hsc-70 interacting protein (CHIP), a molecule involved in metastasis. Profilin1 downregulation also correlates with breast cancer metastasis (Table 1 and Figure 4).…”

Section: Profilin1 In Breast Cancer and Metastasismentioning

confidence: 99%

“…Interestingly, despite profilin1’s involvement in lamellipodium formation and cell motility in healthy cells, CHIP -mediated knockdown of profilin1 in breast cancer cells resulted in a pro-migratory phenotype characterized by abundance of F-actin structure. This event contributed to the ability of the cancer to metastasize in response to lowering of profilin1 levels [70]. Profilin1 also interacts with estrogen receptor alpha (ERα), which is known to mediate apoptosis in certain cell lines, in addition to contributing to metastasis.…”

Section: Profilin1 In Breast Cancer and Metastasismentioning

confidence: 99%

Profilin1 biology and its mutation, actin(g) in disease

Alkam

Feldman

Singh

et al. 2016

Cell. Mol. Life Sci.

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Profilins were discovered in the 1970’s and were extensively studied for their significant physiological roles. Profilin1 is the most prominent isoform and has drawn special attention due to its role in the cytoskeleton, cell signaling, and its link to conditions such as cancer and vascular hypertrophy. Recently, multiple mutations in the profilin1 gene were linked to Amyotrophic Lateral Sclerosis (ALS). In this review, we will discuss the physiological and pathological roles of profilin1. We will further highlight the cytoskeletal function and dysfunction caused by profilin1 dysregulation. Finally, we will discuss the implications of mutant profilin1 in various diseases with an emphasis on its contribution to the pathogenesis of ALS.

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“…As a cochaperone E3 ligase, CHIP has been known for regulating proteins presented by molecular chaperones. However, recent reports presented the possibility that CHIP might use alternative mechanisms to regulate specific protein substrates, as CHIP interacts with specific target proteins independent of molecular chaperones 20 , 23 , 41 , including some direct physical interactions 21 , 22 . In the present study, we found that cIAP1 physically binds to CHIP via its BIR3 domain and to eIF4E via BIR1, which enables CHIP to regulate eIF4E without a chaperone.…”

Section: Discussionmentioning

confidence: 99%

“…However, CHIP has also recently been shown to ubiquitinate specific target proteins for proteasomal degradation 17 – 19 . Interestingly, several reports showed that CHIP is able to regulate certain target proteins in a chaperone-independent manner 20 – 23 , suggesting that the molecular mechanisms of CHIP-driven ubiquitination may be diverse and dependent on the target protein. Although ubiquitination of eIF4E by CHIP has been shown in human cell lines 24 , the precise molecular mechanism by which CHIP regulates eIF4E has yet to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

A novel function of cIAP1 as a mediator of CHIP-driven eIF4E regulation

Seo

Lee

Choi

et al. 2017

Sci Rep

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eIF4E is an initiator protein in cap-dependent translation. Its overexpression is linked to tumorigenesis in various human cancers, suggesting that the levels of eIF4E must be under tight control in normal cells. Although several eIF4E regulatory mechanisms have been demonstrated, the intracellular mechanisms controlling eIF4E protein levels remain poorly understood. Here, we report that eIF4E is efficiently regulated by dual mechanisms, both involving human inhibitor of apoptosis family protein cIAP1. cIAP1 itself ubiquitinates eIF4E as an E3 ligase, and interestingly, cIAP1 also functions as a mediator to present eIF4E to another E3 ligase, CHIP. This collaborative activity of cIAP1 and CHIP directs eIF4E toward degradation, controlling its levels and suppressing tumorigenesis. Our results provide the first evidence for a mediator function of cIAP1 and collaborative activity of cIAP1 and CHIP, suggesting that maintaining balanced levels of these E3 ligases might be beneficial for normal cell growth.

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C-terminus of Hsc70-interacting protein regulates profilin1 and breast cancer cell migration

Cited by 29 publications

References 34 publications

MiR-1178 Promotes the Proliferation, G1/S Transition, Migration and Invasion of Pancreatic Cancer Cells by Targeting CHIP

MiR-1178 Promotes the Proliferation, G1/S Transition, Migration and Invasion of Pancreatic Cancer Cells by Targeting CHIP

Profilin1 biology and its mutation, actin(g) in disease

A novel function of cIAP1 as a mediator of CHIP-driven eIF4E regulation

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