cd15769

FYVE-like domain found in caspase regulator CARP1 and similar proteins

CDD entry
Member databaseCDD
CDD typedomain
Short nameFYVE_CARP1
SetFYVE_like_SF

Description

CARP1, also termed E3 ubiquitin-protein ligase RNF34, or caspases-8 and -10-associated RING finger protein 1, or FYVE-RING finger protein Momo, or RING finger homologous to inhibitor of apoptosis protein (RFI), or RING finger protein 34, or RING finger protein RIFF, is a nuclear protein that functions as a specific E3 ubiquitin ligase for the transcriptional coactivator PGC-1alpha, a master regulator of energy metabolism and adaptive thermogenesis in the brown fat cell, and negatively regulates brown fat cell metabolism. It is preferentially expressed in esophageal, gastric and colorectal cancers, suggesting a possible association with the development of the digestive tract cancers. It regulates the p53 signaling pathway through degrading 14-3-3 sigma and stabilizing MDM2. CARP1 does not localize to membranes in the cell and is involved in the negative regulation of apoptosis, specifically targeting two initiator caspases, caspase 8 and caspase 10, which are distinguished from other FYVE-type proteins. Moreover, CARP1 has an altered sequence in the basic ligand binding patch and lack the WxxD (x for any residue) motif that is conserved only in phosphoinositide binding FYVE domains. Thus it belongs to a family of unique FYVE-type domains called FYVE-like domains. In addition to the N-terminal FYVE-like domain, CARP1 harbors a C-terminal RING domain.
[4, 8, 2, 9, 3, 1, 6, 7, 5, 10]

References

1.High hRFI expression correlates with resistance to fluoropyrimidines in human colon cancer cell lines and in xenografts. Sasaki S, Watanabe T, Kobunai T, Konishi T, Kitayama J, Nagawa H. J Exp Clin Cancer Res 24, 397-403, (2005). PMID: 16270526

2.Overexpression of hRFI (human ring finger homologous to inhibitor of apoptosis protein type) inhibits death receptor-mediated apoptosis in colorectal cancer cells. Konishi T, Sasaki S, Watanabe T, Kitayama J, Nagawa H. Mol Cancer Ther 4, 743-50, (2005). PMID: 15897238

3.Overexpression of hRFI inhibits 5-fluorouracil-induced apoptosis in colorectal cancer cells via activation of NF-kappaB and upregulation of BCL-2 and BCL-XL. Konishi T, Sasaki S, Watanabe T, Kitayama J, Nagawa H. Oncogene 25, 3160-9, (2006). PMID: 16407826

4.Isolation and characterization of a novel gene, hRFI, preferentially expressed in esophageal cancer. Sasaki S, Nakamura T, Arakawa H, Mori M, Watanabe T, Nagawa H, Croce CM. Oncogene 21, 5024-30, (2002). PMID: 12118383

5.Diffuse expression of hRFI is correlated with blood vessel invasion in gastric carcinoma. Sasaki S, Kitayama J, Watanabe T, Konishi T, Nagawa H. Jpn J Clin Oncol 34, 584-7, (2004). PMID: 15591455

6.Exogenous expression of hRFI induces multidrug resistance through escape from apoptosis in colorectal cancer cells. Konishi T, Sasaki S, Watanabe T, Kitayama J, Nagawa H. Anticancer Res 25, 2737-41, (2005). PMID: 16080519

7.Effects of expression of hRFI on adenoma formation and tumor progression in colorectal adenoma-carcinoma sequence. Sasaki S, Watanabe T, Konishi T, Kitayama J, Nagawa H. J Exp Clin Cancer Res 23, 507-12, (2004). PMID: 15595643

8.Suppression of caspase-8- and -10-associated RING proteins results in sensitization to death ligands and inhibition of tumor cell growth. McDonald ER 3rd, El-Deiry WS. Proc Natl Acad Sci U S A 101, 6170-5, (2004). PMID: 15069192

9.RNF34 is a cold-regulated E3 ubiquitin ligase for PGC-1α and modulates brown fat cell metabolism. Wei P, Pan D, Mao C, Wang YX. Mol Cell Biol 32, 266-75, (2012). PMID: 22064484

10.CARPs enhance p53 turnover by degrading 14-3-3sigma and stabilizing MDM2. Yang W, Dicker DT, Chen J, El-Deiry WS. Cell Cycle 7, 670-82, (2008). PMID: 18382127

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