Post-translational Modifications of Three Members of the Human MAP1LC3 Family and Detection of a Novel Type of Modification for MAP1LC3B

He, Hua; Dang, Yongjun; Dai, Fengwei; Guo, Zekun; Wu, Jiaxue; She, Xinyu; Pan, Yuan; Chen, Yongjing; Ling, Wenhai; Wu, Chaoqun; Zhao, Shengming; Liu, Jun O.; Liu, Yu

doi:10.1074/jbc.m303800200

Cited by 265 publications

(228 citation statements)

References 31 publications

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“…8 Furthermore, MAP1LC3C is poorly expressed in tissues, showing a relative prevalence in placenta, lung and ovaries. 7 In our study we were able to detect the mRNA levels of LC3A in liver, kidney and lung mouse tissues and, furthermore, imunohistochemistry confirmed cytoplasmic localization of LC3A in these tissues. Among the three isoforms MAP1LC3A (or simply LC3A) is a well-defined autophagosomal marker with a conserved post-translational modification at the C-terminal Gly120.…”

Section: Resultssupporting

confidence: 66%

“…The MAP1LC3B is expressed in heart, brain, skeletal muscle and testis and least expressed in the liver, where MAP1LC3A is most plentiful. 7 Also, MAP1LC3B is expressed highly in peripheral blood leukocytes in which MAP1LC3A mRNA is absent. 7 In contrast, Wu and coworkers reported that MAP1LC3A is abundant in heart, brain, skeletal muscle, lung and testis and undetectable in liver, pancreas, spleen and small intestine of rat tissues, whereas MAP1LC3B is expressed highly in liver, brain, skeletal muscle and testis but is undetectable in lung.…”

Section: Resultsmentioning

confidence: 99%

“…7 Also, MAP1LC3B is expressed highly in peripheral blood leukocytes in which MAP1LC3A mRNA is absent. 7 In contrast, Wu and coworkers reported that MAP1LC3A is abundant in heart, brain, skeletal muscle, lung and testis and undetectable in liver, pancreas, spleen and small intestine of rat tissues, whereas MAP1LC3B is expressed highly in liver, brain, skeletal muscle and testis but is undetectable in lung. 8 Wu and coworkers revealed that both LC3A and LC3B are associated with the autophagic membranes in rats.…”

Section: Resultsmentioning

confidence: 99%

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"Autophagic flux" in normal mouse tissues: Focus on endogenous LC3A processing

Zois¹,

Giatromanolaki²,

Sivridis³

et al. 2011

Autophagy

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A utophagy is a major intracellular pathway for the degradation and recycling of long-lived proteins, mature ribosomes and even entire organelles. The best-studied autophagic marker is the LC3B protein and it is thought that the amount of LC3B-II correlates with the amount of autophagic membranes. Whether LC3A processing, in addition to LC3B, is a valuable endogenous "autophagic flux'' marker is far less clear. The specificity of rabbit polyclonal antibodies to LC3A and LC3B was tested against the commercial available human recombinant proteins LC3A and LC3B. In order to measure "autophagic flux'' in mouse liver, lung, kidney and heart we used: (1) a lysosomotropic reagent, chloroquine, which inhibits intralysosomal acidification and ultimately their fusion with autophagosomes, (2) nutrient starvation as an autophagic stimulus and (3) ionizing radiation, which destabilizes lysosomes. According to the immunoblotting work, the LC3A protein follows discrete patterns of LC3A-I and LC3A-II changes in liver, lung, kidney and heart tissues of mice, whereas the LC3B protein did not follow the same pattern under stressor conditions. We conclude that the endogenous LC3A processing is a major marker of autophagy flux in the mouse model. Fractionated samples (soluble vs membrane fractions) should be used in immunoblotting to allow discrimination between the soluble LC3-I and the membrane-associated LC3-II proteins and the kinetics of modification. Furthermore, "Autophagic flux" in normal mouse tissues

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Section: Resultssupporting

confidence: 66%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

"Autophagic flux" in normal mouse tissues: Focus on endogenous LC3A processing

Zois¹,

Giatromanolaki²,

Sivridis³

et al. 2011

Autophagy

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show abstract

“…Since knockdown of SRC-3 or MIF reduced Bcl-2 levels, but did not significantly affect apoptosis (Supplementary information, Figure S8), we investigated whether MIF regulated autophagy. Cleavage of the autophagy marker microtubule-associated protein 1 light chain (LC3) to LC3-I and conjugation of LC3-I to phosphatidylethanolamine to form LC3-II is an essential process for the formation of autophagosomal vacuoles [44][45][46][47][48][49]. As the levels of LC3-II are proportional to the extent of autophagic vacuole formation, we therefore examined the processing of LC3 as an indicator of autophagy activity.…”

Section: Mif Regulates Autophagymentioning

confidence: 99%

Steroid receptor coactivator 3 regulates autophagy in breast cancer cells through macrophage migration inhibitory factor

et al. 2012

Cell Res

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SRC-3/AIB1 (steroid receptor coactivator 3/amplified in breast cancer 1) is an authentic oncogene that contributes to the development of drug resistance and poor disease-free survival in cancer patients. Autophagy is also an important cell death mechanism that has tumor suppressor function. In this study, we identified macrophage migration inhibitory factor (MIF) as a novel target gene of SRC-3 and demonstrated its importance in cell survival. Specifically, we showed that MIF is a strong suppressor of autophagic cell death. We further showed that suppression of MIF, in turn, induced autophagic cell death, enhanced chemosensitivity and inhibited tumorigenesis in a xenograft mouse tumorigenesis model. Our study demonstrated that regulation of MIF expression and suppression of autophagic cell death is a potent mechanism by which SRC-3 contributes to increased chemoresistance and tumorigenicity.

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“…Briefly, 5 AL of the total 20 AL of reverse-transcribed product were used for PCR in 1Â PCR buffer containing 1.5 mmol/L MgCl 2 , 250 Amol/L deoxynucleotide triphosphates, 0.5 unit of Taq polymerase (Invitrogen/ Life Technologies), and 100 ng of TG2 primer (primer I, 5 ¶-TA-TGGCCAGTGCTGGGTCTTCGCC-3 ¶; primer II, 5 ¶-GGCTC-CAGGGTTAGGTTGAGCAGG-3 ¶) or PKCy primers (primer I, 5 ¶-CGAAGAGTTCATCCTCATCATA and primer II, 5 ¶-TTTC-TCACCCACCTCATCTG) or h-actin -specific primer (SigmaGenosys, Houston, TX). Semiquantitative RT-PCRs were done using different cycles of PCR (26,30,36) to find optimum PCR cycle that falls in the linear range of amplification. For the TG2 and PKC experiments, 30 PCR cycles were used.…”

Section: Rna Isolation and Rt-pcr Analysismentioning

confidence: 99%

Tissue Transglutaminase Inhibits Autophagy in Pancreatic Cancer Cells

Akar

Özpolat

Mehta

et al. 2007

Molecular Cancer Research

118

107

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Elevated expression of tissue transglutaminase (TG2) in cancer cells has been implicated in the development of drug resistance and metastatic phenotypes. However, the role and the mechanisms that regulate TG2 expression remain elusive. Here, we provide evidence that protein kinase CD (PKCD) regulates TG2 expression, which in turn inhibits autophagy, a type II programmed cell death, in pancreatic cancer cells that are frequently insensitive to standard chemotherapeutic agents. Rottlerin, a PKCD-specific inhibitor, and PKCD small interfering RNA (siRNA) down-regulated the expression of TG2 mRNA and protein and induced growth inhibition without inducing apoptosis in pancreatic cancer cells. Inhibition of PKCD by rottlerin or knockdown of TG2 protein by a TG2-specific siRNA resulted in a marked increase in autophagy shown by presence of autophagic vacuoles in the cytoplasm, formation of the acidic vesicular organelles, membrane association of microtubule-associated protein 1 light chain 3 (LC3) with autophagosomes, and a marked induction of LC3-II protein, important hallmarks of autophagy, and by electron microscopy. Furthermore, inhibition of TG2 by rottlerin or by the siRNA led to accumulation of green fluorescent protein (GFP)-LC3-II in autophagosomes in pancreatic cancer cells transfected with GFP-LC3 (GFP-ATG8) expression vector. Knockdown of Beclin-1, a specific autophagy-promoting protein and the product of Becn1 (ATG6), inhibited rottlerin-induced and TG2 siRNA -induced autophagy, indicating that Beclin-1 is required for this process. These results revealed that PKCD plays a critical role in the expression of TG2, which in turn regulates autophagy. In conclusion, these results suggest a novel mechanism of regulation of TG2 and TG2-mediated autophagy in pancreatic cancer cells.

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Post-translational Modifications of Three Members of the Human MAP1LC3 Family and Detection of a Novel Type of Modification for MAP1LC3B

Cited by 265 publications

References 31 publications

"Autophagic flux" in normal mouse tissues: Focus on endogenous LC3A processing

"Autophagic flux" in normal mouse tissues: Focus on endogenous LC3A processing

Steroid receptor coactivator 3 regulates autophagy in breast cancer cells through macrophage migration inhibitory factor

Tissue Transglutaminase Inhibits Autophagy in Pancreatic Cancer Cells

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