TRIM32: A Multifunctional Protein Involved in Muscle Homeostasis, Glucose Metabolism, and Tumorigenesis

Bawa, Simranjot; Piccirillo, Rosanna; Geisbrecht, Erika R.

doi:10.3390/biom11030408

Cited by 20 publications

(23 citation statements)

References 147 publications

(132 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The E3 ubiquitin ligase tripartite motif containing (Trim) 32 is a ubiquitously expressed multifunctional protein that plays a role in differentiation, tumor suppression, muscle physiology and regeneration [ 167 ]. Similar to MuRF1, it belongs to the TRIM family of proteins, which contain three zinc binding domains composed of a RING-finger, a coiled-coil region and a B-box type 1 and 2 [ 168 ].…”

Section: Protein Turnover In Muscle Is Regulated By a Precisely Acting Protein Degradation Pathwaymentioning

confidence: 99%

Out of Control: The Role of the Ubiquitin Proteasome System in Skeletal Muscle during Inflammation

2021

View full text Add to dashboard Cite

The majority of critically ill intensive care unit (ICU) patients with severe sepsis develop ICU-acquired weakness (ICUAW) characterized by loss of muscle mass, reduction in myofiber size and decreased muscle strength leading to persisting physical impairment. This phenotype results from a dysregulated protein homeostasis with increased protein degradation and decreased protein synthesis, eventually causing a decrease in muscle structural proteins. The ubiquitin proteasome system (UPS) is the predominant protein-degrading system in muscle that is activated during diverse muscle atrophy conditions, e.g., inflammation. The specificity of UPS-mediated protein degradation is assured by E3 ubiquitin ligases, such as atrogin-1 and MuRF1, which target structural and contractile proteins, proteins involved in energy metabolism and transcription factors for UPS-dependent degradation. Although the regulation of activity and function of E3 ubiquitin ligases in inflammation-induced muscle atrophy is well perceived, the contribution of the proteasome to muscle atrophy during inflammation is still elusive. During inflammation, a shift from standard- to immunoproteasome was described; however, to which extent this contributes to muscle wasting and whether this changes targeting of specific muscular proteins is not well described. This review summarizes the function of the main proinflammatory cytokines and acute phase response proteins and their signaling pathways in inflammation-induced muscle atrophy with a focus on UPS-mediated protein degradation in muscle during sepsis. The regulation and target-specificity of the main E3 ubiquitin ligases in muscle atrophy and their mode of action on myofibrillar proteins will be reported. The function of the standard- and immunoproteasome in inflammation-induced muscle atrophy will be described and the effects of proteasome-inhibitors as treatment strategies will be discussed.

show abstract

Section: Protein Turnover In Muscle Is Regulated By a Precisely Acting Protein Degradation Pathwaymentioning

confidence: 99%

Out of Control: The Role of the Ubiquitin Proteasome System in Skeletal Muscle during Inflammation

2021

View full text Add to dashboard Cite

show abstract

“…This phenomenon could be explained by the functional role of TRIM32 as an E3 ligase, the residual of which resulted in increased proteasomal degradation in PDAC cells. 44,45 In summary, our study showed that ibr-7 alone or combined with gemcitabine exhibited potent anti-PDAC activity both in vitro and in vivo via the suppression of mTOR/p70S6K pathway, accompanied with significant downregulation of TRIM32. TRIM32 could form a positive feedback loop with mTOR/p70S6K, dictate malignant properties of PDAC cells and finally affected the drug sensitivity of gemcitabine.…”

Section: Trim32 Played a Key Role In The Progression Of Pdac Cellsmentioning

confidence: 69%

“…This phenomenon could be explained by the functional role of TRIM32 as an E3 ligase, the residual of which resulted in increased proteasomal degradation in PDAC cells. 44 , 45 …”

Section: Discussionmentioning

confidence: 99%

Inhibition of TRIM32 by ibr‐7 treatment sensitizes pancreatic cancer cells to gemcitabine via mTOR/p70S6K pathway

Zhang

Yan

et al. 2021

J Cellular Molecular Medi

View full text Add to dashboard Cite

Pancreatic cancer is one of the most notorious diseases for being asymptomatic at early stage and high mortality rate thereafter. However, either chemotherapy or targeted therapy has rarely achieved success in recent clinical trials for pancreatic cancer. Novel therapeutic regimens or agents are urgently in need. Ibr‐7 is a novel derivative of ibrutinib, displaying superior antitumour activity in pancreatic cancer cells than ibrutinib. In vitro studies showed that ibr‐7 greatly inhibited the proliferation of BxPC‐3, SW1990, CFPAC‐1 and AsPC‐1 cells via the induction of mitochondrial‐mediated apoptosis and substantial suppression of mTOR/p70S6K pathway. Moreover, ibr‐7 was able to sensitize pancreatic cancer cells to gemcitabine through the efficient repression of TRIM32, which was positively correlated with the proliferation and invasiveness of pancreatic cancer cells. Additionally, knockdown of TRIM32 diminished mTOR/p70S6K activity in pancreatic cancer cells, indicating a positive feedback loop between TRIM32 and mTOR/p70S6K pathway. To conclude, this work preliminarily explored the role of TRIM32 in the malignant properties of pancreatic cancer cells and evaluated the possibility of targeting TRIM32 to enhance effectiveness of gemcitabine, thereby providing a novel therapeutic target for pancreatic cancer.

show abstract

“…Drosophila body wall skeletal muscles have emerged as an important model system to determine the mechanisms of muscle growth and differentiation [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34]. Previously, we have found that FoxO overexpression in larval body wall skeletal muscles leads to myofiber atrophy and reduces developmental muscle growth [35], suggesting that the fruit fly Drosophila melanogaster can be used to identify evolutionary-conserved regulators of myofiber size [10,36,37].…”

Section: Introductionmentioning

confidence: 99%

A large-scale transgenic RNAi screen identifies transcription factors that modulate myofiber size in Drosophila

et al. 2021

View full text Add to dashboard Cite

Myofiber atrophy occurs with aging and in many diseases but the underlying mechanisms are incompletely understood. Here, we have used >1,100 muscle-targeted RNAi interventions to comprehensively assess the function of 447 transcription factors in the developmental growth of body wall skeletal muscles in Drosophila. This screen identifies new regulators of myofiber atrophy and hypertrophy, including the transcription factor Deaf1. Deaf1 RNAi increases myofiber size whereas Deaf1 overexpression induces atrophy. Consistent with its annotation as a Gsk3 phosphorylation substrate, Deaf1 and Gsk3 induce largely overlapping transcriptional changes that are opposed by Deaf1 RNAi. The top category of Deaf1-regulated genes consists of glycolytic enzymes, which are suppressed by Deaf1 and Gsk3 but are upregulated by Deaf1 RNAi. Similar to Deaf1 and Gsk3 overexpression, RNAi for glycolytic enzymes reduces myofiber growth. Altogether, this study defines the repertoire of transcription factors that regulate developmental myofiber growth and the role of Gsk3/Deaf1/glycolysis in this process.

show abstract

TRIM32: A Multifunctional Protein Involved in Muscle Homeostasis, Glucose Metabolism, and Tumorigenesis

Cited by 20 publications

References 147 publications

Out of Control: The Role of the Ubiquitin Proteasome System in Skeletal Muscle during Inflammation

Out of Control: The Role of the Ubiquitin Proteasome System in Skeletal Muscle during Inflammation

Inhibition of TRIM32 by ibr‐7 treatment sensitizes pancreatic cancer cells to gemcitabine via mTOR/p70S6K pathway

A large-scale transgenic RNAi screen identifies transcription factors that modulate myofiber size in Drosophila

Contact Info

Product

Resources

About