scholarly journals X-linked Inhibitor of Apoptosis Protein and Its E3 Ligase Activity Promote Transforming Growth Factor-β-mediated Nuclear Factor-κB Activation during Breast Cancer Progression

2009 ◽  
Vol 284 (32) ◽  
pp. 21209-21217 ◽  
Author(s):  
Jason R. Neil ◽  
Maozhen Tian ◽  
William P. Schiemann
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Cancer Progression ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Nuclear Factor Κb ◽  
Inhibitor Of Apoptosis ◽  
Nuclear Factor ◽  
Inhibitor Of Apoptosis Protein ◽  
Apoptosis Protein

scholarly journals X-linked Inhibitor of Apoptosis Protein Functions as a Cofactor in Transforming Growth Factor-β Signaling

2001 ◽  
Vol 276 (28) ◽  
pp. 26542-26549 ◽  
Author(s):  
Stephanie Birkey Reffey ◽  
Jens U. Wurthner ◽  
W. Tony Parks ◽  
Anita B. Roberts ◽  
Colin S. Duckett
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Inhibitor Of Apoptosis ◽  
Inhibitor Of Apoptosis Protein ◽  
Apoptosis Protein ◽  
Protein Functions

Co-activation of synovial fibroblasts by laminin-111 and transforming growth factor-β induces expression of matrix metalloproteinases 3 and 10 independently of nuclear factor-κB

2007 ◽  
Vol 67 (4) ◽  
pp. 559-562 ◽  
Author(s):  
K Warstat ◽  
T Pap ◽  
G Klein ◽  
S Gay ◽  
W K Aicher
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Synovial Fibroblasts ◽  
Transforming Growth Factor Β ◽  
Nuclear Factor Κb ◽  
Mrna Levels ◽  
Nuclear Factor ◽  
The Matrix ◽  
Specific Tissue ◽  
Significant Expression

We showed previously that the attachment of synovial fibroblasts to laminin (LM)-111 in the presence of transforming growth factor-β induces significant expression of the matrix metalloproteinase (MMP)-3. Here we go on to investigate the regulation of additional MMPs and their specific tissue inhibitors of matrix proteases (TIMPs). Changes in steady-state mRNA levels encoding TIMPs and MMPs were investigated by quantitative reverse transcription–polymerase chain reaction. Production of MMPs was monitored by a multiplexed immunoarray. Signal transduction pathways were studied by immunoblotting. Attachment of synovial fibroblasts to LM-111 in the presence of transforming growth factor-β induced significant increases in MMP-3 mRNA (12.35-fold, p<0.001) and protein (mean 62 ng/ml, sixfold, p<0.008) and in expression of MMP-10 mRNA (11.68-fold, p<0.05) and protein (54 ng/ml, 20-fold, p⩾0.02). All other TIMPs and MMPs investigated failed to show this LM-111-facilitated transforming growth factor-β response. No phosphorylation of nuclear factor-κB was observed. We conclude that co-stimulation of synovial fibroblasts by LM-111 together with transforming growth factor-β suffices to induce significant expression of MMP-3 and MMP-10 by synovial fibroblasts and that this induction is independent of nuclear factor-κB phosphorylation.

Cellular inhibitor of apoptosis protein 2 controls human colonic epithelial restitution, migration, and Rac1 activation

2015 ◽  
Vol 308 (2) ◽  
pp. G92-G99 ◽  
Author(s):  
Jakob Benedict Seidelin ◽  
Sylvester Larsen ◽  
Dorte Linnemann ◽  
Ben Vainer ◽  
Mehmet Coskun ◽  
...  
Keyword(s):  
Wound Healing ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Human Colon ◽  
Inhibitor Of Apoptosis ◽  
Experimental Ulcer ◽  
Inhibitor Of Apoptosis Protein ◽  
Apoptosis Protein

Identification of pathways involved in wound healing is important for understanding the pathogenesis of various intestinal diseases. Cellular inhibitor of apoptosis protein 2 (cIAP2) regulates proliferation and migration in nonepithelial cells and is expressed in human colonocytes. The aim of the study was to investigate the role of cIAP2 for wound healing in the normal human colon. Wound tissue was generated by taking rectosigmoidal biopsies across an experimental ulcer in healthy subjects after 5, 24, and 48 h. In experimental ulcers, the expression of cIAP2 in regenerating intestinal epithelial cells (IECs) was increased at the wound edge after 24 h ( P < 0.05), returned to normal after reepithelialization, and correlated with the inflammatory reaction in the experimental wounds ( P < 0.001). cIAP2 was induced in vitro in regenerating Caco2 IECs after wound infliction ( P < 0.01). Knockdown of cIAP2 caused a substantial impairment of the IEC regeneration through inhibition of migration ( P < 0.005). cIAP2 overexpression lead to formation of migrating IECs and upregulation of expression of RhoA and Rac1 as well as GTP-activation of Rac1. Transforming growth factor-β1 enhanced the expression of cIAP2 but was not upregulated in wounds in vivo and in vitro. NF-κB and MAPK pathways did not affect cIAP2 expression. cIAP2 is in conclusion a regulator of human intestinal wound healing through enhanced migration along with activation of Rac1, and the findings suggest that cIAP2 could be a future therapeutic target to improve intestinal wound healing.

scholarly journals Inhibitor of Apoptosis Protein cIAP2 Is Essential for Lipopolysaccharide-Induced Macrophage Survival

2006 ◽  
Vol 26 (2) ◽  
pp. 699-708 ◽  
Author(s):  
Damiano Conte ◽  
Martin Holcik ◽  
Charles A. Lefebvre ◽  
Eric LaCasse ◽  
David J. Picketts ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Potent Inhibitor ◽  
Nuclear Factor Κb ◽  
Innate Immune ◽  
The Other ◽  
Inhibitor Of Apoptosis ◽  
Nuclear Factor ◽  
Inhibitor Of Apoptosis Protein ◽  
Apoptotic Death ◽  
Apoptosis Protein

ABSTRACT The cellular inhibitor of apoptosis 2 (cIAP2/HIAP1) is a potent inhibitor of apoptotic death. In contrast to the other members of the IAP family, cIAP2 is transcriptionally inducible by nuclear factor-κB in response to multiple triggers. We demonstrate here that cIAP2−/− mice exhibit profound resistance to lipopolysaccharide (LPS)-induced sepsis, specifically because of an attenuated inflammatory response. We show that LPS potently upregulates cIAP2 in macrophages and that cIAP2−/− macrophages are highly susceptible to apoptosis in a LPS-induced proinflammatory environment. Hence, cIAP2 is critical in the maintenance of a normal innate immune inflammatory response.

Sign in / Sign up

Export Citation Format

Share Document