Flightless‐I, a gelsolin family member and transcriptional regulator, preferentially binds directly to activated cytosolic CaMK‐II

Seward, Matthew E.; Easley, Charles A.; McLeod, Jamie Josephine Avila; Myers, Alexandra L.; Tombes, Robert M.

doi:10.1016/j.febslet.2008.06.037

Cited by 31 publications

(29 citation statements)

References 41 publications

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“…Flightless-I has been found to inhibit caspase-1 activation as a pseudosubstrate in a manner similar to CrmA, which contains a caspase-1 substrate recognition sequence and functions as an inhibitory substrate1925. Moreover, Flightless-I has an N-terminal leucine-rich repeat (LRR) protein–protein interaction domain that has many identified binding partners, including LRRFIPs, TRIP and CaMK-II12142930. The connection between LRRFIP2–Flightless-I interaction and Flightless-I-mediated caspase-1 inhibition we reported here have revealed the whole picture of Flightless-I interacting proteins.…”

Section: Discussionmentioning

confidence: 99%

LRRFIP2 negatively regulates NLRP3 inflammasome activation in macrophages by promoting Flightless-I-mediated caspase-1 inhibition

Jin

Han

et al. 2013

Nat Commun

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The NLRP3 inflammasome is the most characterized inflammasome activated by cellular infection or stress, which is responsible for the maturation of proinflammatory cytokines IL-1β and IL-18. The precise molecular mechanism for negative regulation of NLRP3 inflammasome activation needs to be further defined. Here we identify leucine-rich repeat Fli-I-interacting protein 2 (LRRFIP2) as an NLRP3-associated protein and an inhibitor for NLRP3 inflammasome activation. LRRFIP2 binds to NLRP3 via its N terminus upon NLRP3 inflammasome activation, and also interacts with Flightless-I, a pseudosubstrate of caspase-1, via its Coil motif. Knockdown of Flightless-I significantly promotes NLRP3 inflammasome activation. LRRFIP2 enhances the interaction between Flightless-I and caspase-1, facilitating the inhibitory effect of Flightless-I on caspase-1 activation. Furthermore, silencing of Flightless-I abrogates the inhibitory effect of LRRFIP2 on NLRP3 inflammasome. These data demonstrate that LRRFIP2 inhibits NLRP3 inflammasome activation by recruiting the caspase-1 inhibitor Flightless-I, thus outlining a new mechanism for negative regulation of NLRP3 inflammasome.

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Section: Discussionmentioning

confidence: 99%

LRRFIP2 negatively regulates NLRP3 inflammasome activation in macrophages by promoting Flightless-I-mediated caspase-1 inhibition

Jin

Han

et al. 2013

Nat Commun

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“…Mutations in this gene are either embryonically lethal or lead to the occurrence of degenerated embryos (Kopecki and Cowin, 2008). More importantly, regarding reproductive aspects, FLiI leads to hormonal co-activation of estrogen, which is fundamental for placental development during pregnancy (Seward et al, 2008).…”

Section: Resultsmentioning

confidence: 99%

Genome wide association study on early puberty in Bos indicus

Nascimento¹,

Matos

Seno

et al. 2016

Genet. Mol. Res.

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ABSTRACT. The aim of this study was to evaluate a genome wide association study (GWAS) approach to identify single nucleotide polymorphisms (SNPs) associated with fertility traits (early puberty) in Nellore cattle (Bos indicus). Fifty-five Nellore cows were selected from a herd monitored for early puberty onset (positive pregnancy at 18 months of age). Extremes of this phenotype were selected; 30 and 25 individuals were pregnant and non-pregnant, respectively, at that age. DNA samples were genotyped using a high-density SNP chip (>777.000 SNP). GWAS using a case-control strategy highlighted a number of significant markers based on their proximity with the Bonferroni correction line. Results indicated that chromosomes 5, 6, 9, 10, and 22 were associated with the traits of interest. The most significant SNPs on these chromosomes were rs133039577, rs110013280, rs134702839, rs109551605, and rs41639155. Candidate genes, as well as quantitative trait loci (QTL) previously reported in the Ensembl and Cattle QTLdb databases, were further investigated. Analysis of the regions close to the SNP on chromosomes 9 and 10 revealed that four QTL had been previously classified under the reproduction category. In conclusion, we have identified SNPs in close proximity to genes associated with reproductive traits. Moreover, U6 spliceosomal RNA was present on three different chromosomes, which is possibly associated with age at first calving, suggesting that it might be a strong candidate for future studies.

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“…In addition to its role as a regulator of the cytoskeleton, the LRR domain allows Flii to bind a number of other proteins unrelated to actin, including LRR Flii interacting proteins 1 and 2 (LRRFIP1 and LRRFIP2) and the double-stranded RNA-binding protein TAR RNA interacting protein (Wilson et al, 1998;Fong and de Couet, 1999). Flii is also involved in numerous cellular activities including regulating transcription via co-activation of nuclear hormone receptors (Archer et al, 2004;Lee et al, 2004) and regulation of b-catenin-dependent transcription (Lee and Stallcup, 2006), important signaling pathways including the Toll-like receptor pathway (Wang et al, 2006;Dai et al, 2009), cellular polarity, asymmetric cell division (Deng et al, 2007), proliferation via interactions with calmodulin-dependent protein kinase type II (Seward et al, 2008), inflammation, and cytokine production via caspase activation and IL-1b maturation (Li et al, 2008).…”

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confidence: 99%

Regeneration of Hair Follicles Is Modulated by Flightless I (Flii) in a Rodent Vibrissa Model

Waters

Lindo

Arkell

et al. 2011

Journal of Investigative Dermatology

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Regeneration of cells, tissues, and organs has long captured the attention of researchers for its obvious potential benefits in biomedical applications. Although mammals are notoriously poor at regeneration compared with many lower-order species, the hair follicle, paradoxically a defining characteristic of mammals, is capable of regeneration following partial amputation. To investigate the role of a negative regulator of wound healing, flightless I (Flii), on hair follicle regeneration, the bulbar region of vibrissae from rats as well as strains of mice expressing low (Flii(+/-)), normal (Flii(+/+)), and high (FLII(Tg/Tg)) levels of Flii were surgically amputated, and then allowed to regenerate in vivo. Macroscopic and histological assessment of the regeneration process revealed impaired or delayed regenerative potential in Flii(+/-) follicles. Regenerated follicles expressing high levels of Flii (FLII(Tg/Tg)) produced significantly longer terminal hair fibers. Immunohistochemical analysis was used to characterize the pattern of expression of Flii, as well as markers of hair follicle development and wound healing-associated factors during hair follicle regeneration. These studies confirmed that Flii appears to have a positive role in the regeneration of hair follicles, contrary to its negative influence on wound healing in skin.

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Flightless‐I, a gelsolin family member and transcriptional regulator, preferentially binds directly to activated cytosolic CaMK‐II

Cited by 31 publications

References 41 publications

LRRFIP2 negatively regulates NLRP3 inflammasome activation in macrophages by promoting Flightless-I-mediated caspase-1 inhibition

LRRFIP2 negatively regulates NLRP3 inflammasome activation in macrophages by promoting Flightless-I-mediated caspase-1 inhibition

Genome wide association study on early puberty in Bos indicus

Regeneration of Hair Follicles Is Modulated by Flightless I (Flii) in a Rodent Vibrissa Model

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