Ubiquitinated annexin A2 is enriched in the cytoskeleton fraction

Lauvrak, Silje Ugland; Hollås, Hanne; Døskeland, Anne P.; Aukrust, Ingvild; Flatmark, Torgeir; Vedeler, Anni

doi:10.1016/j.febslet.2004.11.076

Cited by 28 publications

(21 citation statements)

References 30 publications

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“…The larger molecular weight forms could be a result of ANXA2 ubiquitination as has been observed with extracts from intestinal mucosa (33). Densitometric measurement of the principle ANXA2 band indicated that neither the Cav1 genotype nor the ezetimibe treatment resulted in altered ANXA2 expression levels (WT control diet, 0.18 Ϯ 0.07 density units relative to loading standard ERK1/2; WT EZ, 0.30 Ϯ 0.10; CAV1Ϫ/Ϫ control: 0.24 Ϯ 0.07; CAV1Ϫ/Ϫ EZ, 0.19 Ϯ 0.09, n ϭ 5-6 mice/group).…”

Section: Resultsmentioning

confidence: 99%

Caveolin-1 Is Not Required for Murine Intestinal Cholesterol Transport

Valasek¹,

Weng

Shaul³

et al. 2005

Journal of Biological Chemistry

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Caveolin-1 (CAV1) is the structural protein of the filamentous coat that decorates the cytoplasmic surface of each caveola. Cell culture studies have implicated CAV1 in playing an important role in intracellular cholesterol trafficking. In addition, it has been reported that CAV1 forms a detergent-resistant protein complex with Annexin-2 in enterocytes that can be disrupted by the cholesterol absorption inhibitor ezetimibe, suggesting a possible role for CAV1 in cholesterol absorption. In this report, we have evaluated cholesterol homeostasis in Cav1 knock-out mice. Deletion of CAV1 does not result in either a compensatory increase of CAV2 or CAV3 in intestine. In addition, Cav1 knock-out mice display normal mRNA and protein levels of Annexin-2 or the putative cholesterol transport protein Niemann-Pick C1-like 1 (NPC1L1) in proximal intestinal mucosa. Fractional cholesterol absorption and fecal neutral sterol excretion are statistically similar in Cav1 knock-out mice and their wild-type littermates. Moreover, oral administration of ezetimibe is equally effective in decreasing cholesterol absorption in Cav1 null mice and wild-type controls. The mRNA expression levels of genes sensitive to intracellular cholesterol concentration (ATP-binding cassette transporters ABCA1 and ABCG5, hydroxymethylglutaryl-CoA synthase and the LDL receptor) are similarly altered in the proximal intestinal mucosa of Cav1 null and wild-type mice following ezetimibe treatment. These results demonstrate that CAV1 is not required for cholesterol absorption or ezetimibe sensitivity in the mouse.

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Section: Resultsmentioning

confidence: 99%

Caveolin-1 Is Not Required for Murine Intestinal Cholesterol Transport

Valasek¹,

Weng

Shaul³

et al. 2005

Journal of Biological Chemistry

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“…In contrast, although annexin A2 is ubiquitinated, ubiquitination does not activate the proteasomal degradation of the protein. 42 We have observed that the proteasomal inhibitor MG-132 does not affect the annexin A2 levels (supplemental Figure 1), thereby eliminating proteasomal degradation as a possible mechanism. However, it is known that annexin A2 is mainly cytosolic, whereas the annexin A2-S100A10 complex is associated with the cytoskeleton.…”

Section: Discussionmentioning

confidence: 99%

S100A10 regulates plasminogen-dependent macrophage invasion

O’Connell¹,

Surette²,

Liwski

et al. 2010

Blood

126

148

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The plasminogen activation system plays an integral role in the migration of macrophages in response to an inflammatory stimulus, and the binding of plasminogen to its cell-surface receptor initiates this process. Although previous studies from our laboratory have shown the importance of the plasminogen receptor S100A10 in cancer cell plasmin production, the potential role of this protein in macrophage migration has not been investigated. Using thioglycollate to induce a peritoneal inflammatory response, we demonstrate, for the first time, that compared with wild-type (WT) mice, macrophage migration across the peritoneal membrane into the peritoneal cavity in S100A10-deficient (S100A10 ؊/؊ ) mice was decreased by up to 53% at 24, 48, and 72 hours. Furthermore, the number of S100A10-deficient macrophages that infiltrated Matrigel plugs was reduced by 8-fold compared with their WT counterpart in vivo. Compared with WT macrophages, macrophages from S100A10 ؊/؊ mice demonstrated a 50% reduction in plasmin-dependent invasion across a Matrigel barrier and a 45% reduction in plasmin generation in vitro. This loss in plasmin-dependent invasion was in part the result of a decreased generation of plasmin and a decreased activation of pro-MMP-9 by S100A10-deficient macrophages. This study establishes a direct involvement of S100A10 in macrophage recruitment in response to inflammatory stimuli. (Blood. 2010;116(7): 1136-1146) IntroductionMonocytes/macrophages play a central role in pathogenic inflammatory responses associated with atherosclerosis, restenosis, tumor surveillance, and arthritis. [1][2][3] In response to changes in the cellular environment, monocytes and monocytoid cells undergo extensive phenotypic alterations, including marked changes in their fibrinolytic properties. Synthesis and activation of matrix-degrading proteinases by monocytes and macrophages play an essential role in their migration through tissue. A key proteinase that participates in pericellular proteolysis is the serine proteinase plasmin. Plasmin is a broad substrate proteinase that is formed from the inactive zymogen plasminogen (Plg) by the Plg activators, tissue Plg activator (tPA) and urokinase-type Plg activator (uPA). 4,5 The participation of plasmin in cell invasion and migration is dependent on the ability of plasmin not only to degrade extracellular matrix (ECM) proteins but to also activate other proteinases that have matrix-degrading activity. Plasmin can degrade a variety of matrix proteins, such as laminin and fibronectin, and appears to activate matrix metalloproteinase-1 (MMP-1), MMP-3, and MMP-13 directly, and to activate MMP-2 and MMP-9 indirectly, thereby facilitating cell migration through ECMs. 6 The assembly of Plg and its activators on the cell surface is facilitated by the protein S100A10 (also referred to as p11). S100A10 is a member of the S100 family of calcium-binding proteins and is typically found in most cells bound to its annexin A2 (p36) ligand as the heterotetrameric (S100A10) 2 -(annexin A2) 2 complex, annexi...

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“…Interestingly this modification does not result in proteosomal degradation of annexin A2; rather it promotes its enrichment in the cytoskeletal fraction. This potentially has a role in F-actin and lipid raft binding due to the association of the ubiquitinated form with triton-insoluble fractions [66]. In a recent study by Deng et al [67] the poly-ubiquitinated annexin A2 was shown to be elevated in breast cancer tissue although the functional significance of this observation is not established.…”

Section: Post-translation Modification and Regulation Of Annexin A2mentioning

confidence: 99%

Annexin A2 Heterotetramer: Structure and Function

Bharadwaj

Bydoun

Holloway

et al. 2013

IJMS

249

346

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Annexin A2 is a pleiotropic calcium- and anionic phospholipid-binding protein that exists as a monomer and as a heterotetrameric complex with the plasminogen receptor protein, S100A10. Annexin A2 has been proposed to play a key role in many processes including exocytosis, endocytosis, membrane organization, ion channel conductance, and also to link F-actin cytoskeleton to the plasma membrane. Despite an impressive list of potential binding partners and regulatory activities, it was somewhat unexpected that the annexin A2-null mouse should show a relatively benign phenotype. Studies with the annexin A2-null mouse have suggested important functions for annexin A2 and the heterotetramer in fibrinolysis, in the regulation of the LDL receptor and in cellular redox regulation. However, the demonstration that depletion of annexin A2 causes the depletion of several other proteins including S100A10, fascin and affects the expression of at least sixty-one genes has confounded the reports of its function. In this review we will discuss the annexin A2 structure and function and its proposed physiological and pathological roles.

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Ubiquitinated annexin A2 is enriched in the cytoskeleton fraction

Cited by 28 publications

References 30 publications

Caveolin-1 Is Not Required for Murine Intestinal Cholesterol Transport

Caveolin-1 Is Not Required for Murine Intestinal Cholesterol Transport

S100A10 regulates plasminogen-dependent macrophage invasion

Annexin A2 Heterotetramer: Structure and Function

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