Connexin43 Functions as a Novel Interacting Partner of Heat Shock Cognate Protein 70

Hatakeyama, Tomoya; Dai, Pengcheng; Harada, Yoshinori; Hino, Hitoshi; Tsukahara, Fujiko; Maru, Yoshiro; Otsuji, Eigo; Takamatsu, Tetsuro

doi:10.1038/srep02719

Cited by 28 publications

(25 citation statements)

References 48 publications

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“…Likewise, Cx43 has been shown to inhibit G1/S phase transition by increasing p27 expression in a variety of cancer cell lines (Zhang et al, 2001;Zhang et al, 2003). Recently, Cx43 was found to interact with heat shock cognate protein 70, thereby preventing the nuclear translocation of cyclin D1 and inhibiting G1/S phase transition (Hatakeyama et al, 2013). In addition to modulating cell cycle regulatory proteins, studies suggest that Cx43 interacts with the scaffold protein caveolin-1 (Schubert et al, 2002), and that this interaction contributes to the regulation of cell invasiveness by Cx43 in keratinocytes and glioblastoma cells (Langlois et al, 2010;Strale et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

EGF‐Induced Connexin43 Negatively Regulates Cell Proliferation in Human Ovarian Cancer

Qiu

Cheng

Klausen

et al. 2015

Journal Cellular Physiology

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Connexin43 (Cx43) has been shown to regulate cell proliferation and its downregulation is correlated with poor prognosis and survival in several types of human cancer. Cx43 expression levels are frequently downregulated in human ovarian cancer, suggesting a potential role for Cx43 in regulating the progression of this disease. Epidermal growth factor (EGF) is a well-characterized hormone that stimulates ovarian cancer cell proliferation. Although EGF is able to regulate Cx43 expression in other cell types, it is unclear whether EGF can regulate Cx43 expression in ovarian cancer cells. Additionally, it remains unknown whether Cx43 is involved in EGF-stimulated ovarian cancer cell proliferation. In the present study, we demonstrate that treatment with EGF upregulates Cx43 expression in two ovarian cancer cell lines, SKOV3 and OVCAR4. Although treatment with EGF activates both ERK1/2 and Akt signaling pathways, pharmacological inhibition and siRNA-mediated knockdown suggest that only the activation of Akt1 is required for EGF-induced Cx43 upregulation. Functionally, Cx43 knockdown enhanced basal and EGF-induced cell proliferation, whereas the proliferative effects of EGF were reduced by Cx43 overexpression. Co-treatment with the gap junction inhibitor carbenoxolone did not alter the suppressive effects of Cx43 overexpression on EGF-induced cell proliferation, suggesting a gap junction-independent mechanism. This study reveals an important role for Cx43 as a negative regulator of EGF-induced human ovarian cancer cell proliferation.

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Section: Discussionmentioning

confidence: 99%

EGF‐Induced Connexin43 Negatively Regulates Cell Proliferation in Human Ovarian Cancer

Qiu

Cheng

Klausen

et al. 2015

Journal Cellular Physiology

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“…Hsc70 is a positive regulator of cell cycle transition and carcinogenesis, regulating nuclear accumulation of cyclin D1 along with Connexin43 (Cx43) (125). It is a stress-induced molecule that is both constitutively expressed (Hsc70c) and inducible (Hsc70i), and interacts with an E3 ubiquitin ligase partner, called C-terminus of Hsc70 Interacting Protein (CHIP) (126).…”

Section: Putting On the Brakes: Negative Regulation Of Non-canonical mentioning

confidence: 99%

Emerging Roles for Noncanonical NF-κB Signaling in the Modulation of Inflammatory Bowel Disease Pathobiology

McDaniel

Eden

Ringel

et al. 2016

Inflammatory Bowel Diseases

138

105

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Crohn’s disease and ulcerative colitis are common and debilitating manifestations of inflammatory bowel disease (IBD). IBD is characterized by a radical imbalance in the activation of pro-inflammatory and anti-inflammatory signaling pathways in the gut. These pathways are controlled by NF-κB, which is a master regulator of gene transcription. In IBD patients, NF-κB signaling is often dysregulated resulting in overzealous inflammation. NF-κB activation occurs through two distinct pathways, defined as either canonical or non-canonical. Canonical NF-κB pathway activation is well studied in IBD and is associated with the rapid, acute production of diverse pro-inflammatory mediators, such as COX-2, IL-1β, and IL-6. In contrast to the canonical pathway, the non-canonical or “alternative” NF-κB signaling cascade is tightly regulated and is responsible for the production of highly specific chemokines that tend to be associated with less acute, chronic inflammation. There is a relative paucity of literature regarding all aspects of non-canonical NF-κB signaling. However, it is clear that this alternative signaling pathway plays a considerable role in maintaining immune system homeostasis and likely contributes significantly to the chronic inflammation underlying IBD. Non-canonical NF-κB signaling may represent a promising new direction in the search for therapeutic targets and biomarkers associated with IBD. However, significant mechanistic insight is still required to translate the current basic science findings into effective therapeutic strategies.

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“…NOV/CCN3, Kir6.1, cytoskeletal proteins, etc (Giepmans, 2006;Gellhaus et al, 2010;Ahmad Waza et al, 2012;Hatakeyama et al, 2013). Besides having junctional properties, Cx43 is also an important player in regulating cell growth and differentiation (Araya et al, 2005), with an established tumor suppressive properties (Kandouz et al, 2013).…”

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confidence: 99%

Pathological Implications of Cx43 Down-regulation in Human Colon Cancer

Ismail¹,

Rashid²,

Andrabi³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Connexin43 Functions as a Novel Interacting Partner of Heat Shock Cognate Protein 70

Cited by 28 publications

References 48 publications

EGF‐Induced Connexin43 Negatively Regulates Cell Proliferation in Human Ovarian Cancer

EGF‐Induced Connexin43 Negatively Regulates Cell Proliferation in Human Ovarian Cancer

Emerging Roles for Noncanonical NF-κB Signaling in the Modulation of Inflammatory Bowel Disease Pathobiology

Pathological Implications of Cx43 Down-regulation in Human Colon Cancer

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