Neuromuscular abundance of RB1CC1 contributes to the non-proliferating enlarged cell phenotype through both RB1 maintenance and TSC1 degradation

Chano, Tokuhiro; Saji, Masashi; Inoue, Hirokazu; Minami, Kahori; Kobayashi, Toshiyuki; Hino, Okio; Okabe, Hidetoshi

doi:10.3892/ijmm.18.3.425

Cited by 21 publications

(40 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, different mechanisms were proposed in these studies. Although our study suggests that FIP200 functions to regulate TSC1-TSC2 complex formation [11], the other study shows that FIP200 inhibits TSC by promoting TSC1 degradation through the ubiquitin-proteasomal pathway [15]. These suggest that FIP200 might regulate TSC function differentially under different contexts or in different cell types.…”

Section: Fip200 Function In Protein Synthesis and Cell Growthcontrasting

confidence: 66%

“…Knockdown of FIP200 decreases mTOR activation and cell size whereas overexpression of FIP200 promotes mTOR activation and cell growth under nutrient deprived condition. Importantly, RNAi knockdown of FIP200 in mouse muscle cells reduces the cell size, suggesting that FIP200 might play a role in the regulation of muscle hypertrophy/ atrophy in vivo [15]. Overall, the consensus from these two independent studies is that FIP200 functions to positively regulate mTOR signaling and cell growth through its interaction with TSC1 and inhibition of TSC1-TSC2 complex function and that FIP200 might function in the nutrient signaling pathway to regulate cell growth.…”

Section: Fip200 Function In Protein Synthesis and Cell Growthmentioning

confidence: 99%

“…So far, totally 8 proteins have been identified as FIP200 interacting proteins, including stathmin [6], Pyk2 [3], FAK [13], ActA [7], p53 [14], TSC1 [11,15], ASK1 and TRAF2 [12] (Table 1). It should be noted that not all FIP200 interacting proteins have been confirmed at the endogenous level and therefore the significance of some interactions should be more rigorously studied.…”

Section: Fip200 Function In Various Cellular Processesmentioning

confidence: 99%

“…Finally, it seems that FIP200 plays very diverse biochemical functions with different binding partners (Table 1). FIP200 functions to directly inhibit FAK and Pyk2 kinase activities [3,13], disrupt TSC1-TSC2 complex formation [11], regulate p53 and TSC1 protein stability [14,15], serve as a scaffolding to facilitate TRAF2-ASK1 signaling to JNK activation [12], and regulate the transcription of Rb1 when localizing in nucleus [4]. Since most of these binding partners associate with different regions of FIP200 (Figure 1), it is possible that FIP200 can exert multiple biochemical functions through different domains.…”

Section: Fip200 Function In Various Cellular Processesmentioning

confidence: 99%

“…In addition, FIP200 was shown to be important in nutrient stimulation-induced, but not energyor serum-induced, mTOR activation [11]. Intriguingly, FIP200 was also independently identified as the regulator of TSC-mTOR signaling by a different approach [15]. It was noticed that the expression level of FIP200 is high in large cell types such as neuromuscular cells, but low in smaller cells such as leukocytes, suggesting the potential function of FIP200 in the regulation of cell size.…”

Section: Fip200 Function In Protein Synthesis and Cell Growthmentioning

confidence: 99%

See 4 more Smart Citations

FIP200, a key signaling node to coordinately regulate various cellular processes

Gan

Guan

2008

Cellular Signalling

View full text Add to dashboard Cite

A central question in cell biology is how various cellular processes are coordinately regulated in normal cell and how dysregulation of the normal signaling pathways leads to diseases such as cancer. Recent studies have identified FIP200 as a crucial signaling component to coordinately regulate different cellular events by its interaction with multiple signaling pathways. This review will focus on the cellular functions of FIP200 and its interacting proteins, as well as the emerging roles of FIP200 in embryogenesis and cancer development. Further understanding of FIP200 function might provide novel therapeutic targets for human diseases such as cancer.

show abstract

Section: Fip200 Function In Protein Synthesis and Cell Growthcontrasting

confidence: 66%

Section: Fip200 Function In Protein Synthesis and Cell Growthmentioning

confidence: 99%

Section: Fip200 Function In Various Cellular Processesmentioning

confidence: 99%

Section: Fip200 Function In Various Cellular Processesmentioning

confidence: 99%

Section: Fip200 Function In Protein Synthesis and Cell Growthmentioning

confidence: 99%

See 3 more Smart Citations

FIP200, a key signaling node to coordinately regulate various cellular processes

Gan

Guan

2008

Cellular Signalling

View full text Add to dashboard Cite

show abstract

RB1CC1 activates the promoter and expression of RB1 in human cancer

Ikebuchi

Chano

Ochi

et al. 2009

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

RB1-inducible coiled-coil 1 (RB1CC1, also known as FIP200) is a tumor suppressor implicated in the regulation of RB1 (retinoblastoma 1) expression. However, the molecular mechanism of RB1 regulation by RB1CC1 has not been elucidated. Here, we demonstrate that nuclear RB1CC1 binds to the RB1 promoter using chromatin immunoprecipitation assays with anti-RB1CC1 antibody. Luciferase assays with RB1 promoter reporter plasmids revealed that RB1CC1 activated the RB1 promoter through the 201 bp upstream GC-rich region (from the initiation ATG). Electrophoretic mobility shift assay and Western blot analysis supported RB1CC1 binding to the GC-rich region of the RB1 promoter. In addition, the C-terminus of RB1CC1 was required for nuclear localization and subsequent RB1 promoter activation. Furthermore, the expression levels of RB1CC1 and RB1 significantly correlated with in vivo breast cancer tissues as determined by immunohistochemical analysis. These data indicate that nuclear RB1CC1 directly activates the RB1 promoter to enhance RB1 expression in cancer cells. Evaluation of RB1CC1 in various types of human cancer tissues is expected to provide useful information for clinical practice and future therapeutic strategies. ' UICCKey words: RB1CC1; RB1; promoter; transcription The RB1-encoded protein (RB1) is a well-known cell cycle regulator, particularly of G1/S-phase cell cycle progression, 1 and also facilitates cellular differentiation. 2 RB1 is believed to be expressed constitutively in various mammalian tissues, though its expression level often varies in a tissue-specific manner. 3 RB1 plays various roles depending on its phosphorylated state, 1 and the regulation of RB1 phosphorylation has been widely studied. However, its transcriptional regulation is poorly understood. 1 Thus, the regulatory mechanism of RB1 expression should be analyzed more thoroughly.RB1-inducible coiled-coil 1 (RB1CC1: the symbol referred to here and approved by the Human Genome Organization [HUGO] Gene Nomenclature Committee; also known as FIP200, focal adhesion kinase family interacting protein of 200 kDa) was identified as an RB1 regulator and was shown to enhance RB1 expression. 3,4 RB1CC1 functions in various processes such as cell growth, 5,6 proliferation, 3,4,7 apoptosis 8 and autophagy. 9 Mutated RB1CC1 lacking wild-type function has been detected in breast cancers, 4,10 and its functional loss resulted in RB1 repression. Moreover, RNAi-mediated knock down of RB1CC1 leads to reduced RB1 levels and resulted in failure of C2C12 myoblast differentiation. 11 However, the molecular mechanism of RB1CC1 in the RB1 pathway has not been precisely determined yet.In our study, the mechanism of RB1CC1 as a transcriptional regulator of RB1 was investigated. Consequently, it was identified that RB1CC1 binds to and activates the RB1 promoter. The C-terminus of RB1CC1 was essential for its nuclear localization and RB1 promoter activation. Additionally, RB1CC1 status significantly correlated with RB1 expression in in vivo human cancers. Material and ...

show abstract

Tumour Hypoxia and the Hypoxia-Inducible Transcription Factors: Key Players in Cancer Progression and Metastasis

Jögi

2015

Tumor Cell Metabolism

View full text Add to dashboard Cite

Neuromuscular abundance of RB1CC1 contributes to the non-proliferating enlarged cell phenotype through both RB1 maintenance and TSC1 degradation

Cited by 21 publications

References 23 publications

FIP200, a key signaling node to coordinately regulate various cellular processes

FIP200, a key signaling node to coordinately regulate various cellular processes

RB1CC1 activates the promoter and expression of RB1 in human cancer

Tumour Hypoxia and the Hypoxia-Inducible Transcription Factors: Key Players in Cancer Progression and Metastasis

Contact Info

Product

Resources

About