C1-Ten Is a Protein Tyrosine Phosphatase of Insulin Receptor Substrate 1 (IRS-1), Regulating IRS-1 Stability and Muscle Atrophy

Koh, Ara; Lee, Mi Nam; Yang, Yong Ryoul; Jeong, Heeyoon; Ghim, Jaewang; Noh, Jeongeun; Kim, Jaeyoon; Ryu, Dongryeol; Park, Sehoon; Song, Parkyong; Koo, Seung Hoi; Leslie, Nicholas R.; Berggren, Per Olof; Choi, Jang Hyun; Suh, Pann Ghill; Ryu, Sung Ho

doi:10.1128/mcb.01447-12

Cited by 30 publications

(62 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the absence of TNS2, elevated IRS1 signaling may promote tumorigenicity in cancer cells. This is consistent with recent finding that TNS2 acts as a protein tyrosine phosphatase of IRS1 and dephosphorylation of pY612 of IRS1 by TNS2 accelerates IRS1 degradation [26]. Our studies further suggest that TNS2 may suppress IRS1 S616 phosphorylation through regulating Mek and possibly also Akt activities.…”

Section: Discussionsupporting

confidence: 93%

Down-regulation of tensin2 enhances tumorigenicity and is associated with a variety of cancers

et al. 2016

View full text Add to dashboard Cite

Tensin family members, including tensin2 (TNS2), are present as major components of the focal adhesions. The N-terminal end of TNS2 contains a C1 region (protein kinase C conserved region 1) that is not found in other tensin members. Three isoforms of TNS2 have been identified with previous reports describing the shortest V3 isoform as lacking the C1 region. Although TNS2 is known to regulate cell proliferation and migration, its role in tumorigenicity is controversial. By gain-of-function overexpression approaches, results supporting either promotion or reduction of cancer cell tumorigenicity were reported. Here we report that the complete V3 isoform also contains the C1 region and describe the expression patterns of the three human TNS2 isoforms. By loss-of-function approaches, we show that silencing of TNS2 up-regulates the activities of Akt, Mek, and IRS1, and increases tumorigenicities in A549 and Hela cells. Using public database analyses we found that TNS2 is down-regulated in head and neck, esophageal, breast, lung, liver, and colon cancer. In addition, patients with low TNS2 expression showed poor relapse-free survival rates for breast and lung cancers. These results strongly suggest a role of tensin2 in suppressing cell transformation and reduction of tumorigenicity.

show abstract

Section: Discussionsupporting

confidence: 93%

Down-regulation of tensin2 enhances tumorigenicity and is associated with a variety of cancers

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Increased protein breakdown, which exceeds protein synthesis, is a major contributor to critical illness-associated muscle wasting. Inflammatory response and insulin resistance play important roles in muscle wasting by increasing the expression of Murf1 and atrogin-1 [8, 9, 17, 18]. Our previous studies have shown that iNOS deficiency inhibits stress (e.g., burn injury)- and obesity-induced insulin resistance in skeletal muscle [12, 13].…”

Section: Discussionmentioning

confidence: 99%

iNOS as a Driver of Inflammation and Apoptosis in Mouse Skeletal Muscle after Burn Injury: Possible Involvement of Sirt1 S-Nitrosylation-Mediated Acetylation of p65 NF-κB and p53

et al. 2017

View full text Add to dashboard Cite

Inflammation and apoptosis develop in skeletal muscle after major trauma, including burn injury, and play a pivotal role in insulin resistance and muscle wasting. We and others have shown that inducible nitric oxide synthase (iNOS), a major mediator of inflammation, plays an important role in stress (e.g., burn)-induced insulin resistance. However, it remains to be determined how iNOS induces insulin resistance. Moreover, the interrelation between inflammatory response and apoptosis is poorly understood, although they often develop simultaneously. Nuclear factor (NF)-κB and p53 are key regulators of inflammation and apoptosis, respectively. Sirt1 inhibits p65 NF-κB and p53 by deacetylating these transcription factors. Recently, we have shown that iNOS induces S-nitrosylation of Sirt1, which inactivates Sirt1 and thereby increases acetylation and activity of p65 NF-κB and p53 in various cell types, including skeletal muscle cells. Here, we show that iNOS enhances burn-induced inflammatory response and apoptotic change in mouse skeletal muscle along with S-nitrosylation of Sirt1. Burn injury induced robust expression of iNOS in skeletal muscle and gene disruption of iNOS significantly inhibited burn-induced increases in inflammatory gene expression and apoptotic change. In parallel, burn increased Sirt1 S-nitrosylation and acetylation and DNA-binding capacity of p65 NF-κB and p53, all of which were reversed or ameliorated by iNOS deficiency. These results indicate that iNOS functions not only as a downstream effector but also as an upstream enhancer of burn-induced inflammatory response, at least in part, by Sirt1 S-nitrosylation-dependent activation (acetylation) of p65 NF-κB. Our data suggest that Sirt1 S-nitrosylation may play a role in iNOS-mediated enhanced inflammatory response and apoptotic change, which, in turn, contribute to muscle wasting and supposedly to insulin resistance after burn injury.

show abstract

“…Glucocorticoid-treatment consistently leads to a decrease in the amount of IRS-1 protein and inactivation of IRS-1 by serine-phosphorylation (ser307) in vitro in C 2 C 12 myotubes [ 98 -100 ]. Acceleration of the degradation of IRS-1 could come about through multiple mechanisms involving either an increase in the amount of the tyrosine phosphatase, C1-Ten [ 101 ] or the E3 ubiquitin ligase, Cblb [ 98 ].…”

Section: Anti-anabolic Effects Of Glucocorticoidsmentioning

confidence: 99%

Glucocorticoids and Skeletal Muscle

Bodine

Furlow

2015

Advances in Experimental Medicine and Biology

114

View full text Add to dashboard Cite

Glucocorticoids are known to regulate protein metabolism in skeletal muscle, producing a catabolic effect that is opposite that of insulin. In many catabolic diseases, such as sepsis, starvation, and cancer cachexia, endogenous glucocorticoids are elevated contributing to the loss of muscle mass and function. Further, exogenous glucocorticoids are often given acutely and chronically to treat inflammatory conditions such as asthma, chronic obstructive pulmonary disease, and rheumatoid arthritis, resulting in muscle atrophy. This chapter will detail the nature of glucocorticoid-induced muscle atrophy and discuss the mechanisms thought to be responsible for the catabolic effects of glucocorticoids on muscle.

show abstract

C1-Ten Is a Protein Tyrosine Phosphatase of Insulin Receptor Substrate 1 (IRS-1), Regulating IRS-1 Stability and Muscle Atrophy

Cited by 30 publications

References 57 publications

Down-regulation of tensin2 enhances tumorigenicity and is associated with a variety of cancers

Down-regulation of tensin2 enhances tumorigenicity and is associated with a variety of cancers

iNOS as a Driver of Inflammation and Apoptosis in Mouse Skeletal Muscle after Burn Injury: Possible Involvement of Sirt1 S-Nitrosylation-Mediated Acetylation of p65 NF-κB and p53

Glucocorticoids and Skeletal Muscle

Contact Info

Product

Resources

About