KLHL7 (7p15.3),CISS3, SBB126. Nucleolus-säätelijä

https://www.ncbi.nlm.nih.gov/gene/55975

Also known as CISS3; KLHL6; SBBI26

Summary: This gene encodes a BTB-Kelch-related protein. The encoded protein may be involved in protein degradation. Mutations in this gene have been associated with retinitis pigmentosa 42 ( https://www.ncbi.nlm.nih.gov/gtr/conditions/C2751986/ ). [provided by RefSeq, Feb 2010]

Expression: Broad expression in heart (RPKM 18.6), testis (RPKM 12.2) and 24 other tissues See more Orthologs: mouse all

 

CISS3, Cold induced sweating syndrome 

Preferred Names kelch-like protein 7

Names

kelch-like 6

kelch-like 7

kelch/BTB

Related articles in PubMed

1. Clinical and biological roles of Kelch-like family member 7 in breast cancer: a marker of poor prognosis. Kurozumi S, et al. Breast Cancer Res Treat, 2018 Aug. PMID 29633055. The functions of many proteins are tightly regulated with a complex array of cellular functions including ubiquitination. In cancer cells, aberrant ubiquitination may promote the activity of oncogenic pathways with subsequent tumour progression. Kelch-like family member 7 (KLHL7) is involved in the regulation of ubiquitination and may play a role in breast cancer (BC). Present study aims to evaluate the biological and clinical usefulness of KLHL7 in BC utilising large well-characterised cohorts with long-term follow-up..KLHL7 copy number alteration CNA was significantly correlated with its mRNA expression. KLHL7 mRNA expression was higher in luminal B and basal-like molecular subtypes and in higher grade tumours. Increased KLHL7 protein expression was significantly correlated with features of aggressive phenotype including lymphovascular invasion, high histological grade, hormonal receptor negativity, high PIK3CA and p53 expression. Outcome analysis showed that high KLHL7 expression is an independent predictor of shorter survival (p = 0.0011). CONCLUSIONS:
   KLHL7 appears to play an important role in BC progression. High KLHL7 protein expression identified a subgroup of BC with aggressive behaviour and provided independent prognostic information.
   
2. Expanding the clinical spectrum of recessive truncating mutations of KLHL7 to a Bohring-Opitz-like phenotype. Bruel AL, et al. J Med Genet, 2017 Dec. PMID 29074562To expand the phenotypical spectrum of autosomal recessive variants of KLHL7, reported as causing Crisponi syndrome/cold-induced sweating syndrome type 1 (CS/CISS1)-like syndrome.
3. Phenotypic characterization of 3 families with autosomal dominant retinitis pigmentosa due to mutations in KLHL7. Wen Y, et al. Arch Ophthalmol, 2011 Nov. PMID 22084217, Free PMC Article
4. Phenotype associated with mutation in the recently identified autosomal dominant retinitis pigmentosa KLHL7 gene. Hugosson T, et al. Arch Ophthalmol, 2010 Jun. PMID 20547956
5. Mutations in a BTB-Kelch protein, KLHL7, cause autosomal-dominant retinitis pigmentosa. Friedman JS, et al. Am J Hum Genet, 2009 Jun. PMID 19520207, Free PMC Article

See all (28) citations in PubMed

https://www.ncbi.nlm.nih.gov/pubmed/21828050 

 Substrate-specific protein degradation mediated by the ubiquitin proteasome system (UPS) is crucial for the proper function of the cell. Proteins are specifically recognized and ubiquitinated by the ubiquitin ligases (E3s) and are then degraded by the proteasome. BTB proteins act as the substrate recognition subunit that recruits their cognate substrates to the Cullin 3-based multisubunit E3s. Recently, it was reported that missense mutations in KLHL7, a BTB-Kelch protein, are related to autosomal dominant retinitis pigmentosa (adRP). However, the involvement of KLHL7 in the UPS and the outcome of the adRP causative mutations were unknown. In this study, we show that KLHL7 forms a dimer, assembles with Cul3 through its BTB and BACK domains, and exerts E3 activity. Lys-48-linked but not Lys-63-linked polyubiquitin chain co-localized with KLHL7, which increased upon proteasome inhibition suggesting that KLHL7 mediates protein degradation via UPS. An adRP-causative missense mutation in the BACK domain of KLHL7 attenuated only the Cul3 interaction but not dimerization. Nevertheless, the incorporation of the mutant as a heterodimer in the Cul3-KLHL7 complex diminished the E3 ligase activity. Together, our results suggest that KLHL7 constitutes a Cul3-based E3 and that the disease-causing mutation inhibits ligase activity in a dominant negative manner, which may lead to the inappropriate accumulation of the substrates targeted for proteasomal degradation.

 https://www.ncbi.nlm.nih.gov/pubmed/29032201

Kelch-like protein 7 (KLHL7) is a component of Cul3-based Cullin-RING ubiquitin ligase. Recent studies have revealed that mutations in klhl7 gene cause several disorders, such as retinitis pigmentosa (RP). Although KLHL7 is considered to be crucial for regulating the protein homeostasis, little is known about its biological functions.
 In this study, we report that KLHL7 increases terminal uridylyl transferase 1 (TUT1) ubiquitination involved in nucleolar integrity. TUT1 is normally localized in nucleolus; however, expression of KLHL7 facilitates a vulnerability of nucleolar integrity, followed by a decrease of TUT1 localization in nucleolus. On the other hand, pathogenic KLHL7 mutants, which causes an onset of RP, have little effect on both nucleolar integrity and TUT1 localization. Finally, KLHL7 increases TUT1 ubiquitination levels. Taken together, these results imply that KLHL7 is a novel regulator of nucleolus associated with TUT1 ubiquitination. Our study may provide a valuable information to elucidate a pathogenic mechanism of RP.

Copyright © 2017 Elsevier Inc. All rights reserved.KEYWORDS:

KLHL7; Nucleolus; Retinitis pigmentosa; TUT1; UbiquitinPMID:

29032201

DOI:

10.1016/j.bbrc.2017.10.049

[Indexed for MEDLINE]