Kelch Like proteins =KLHL. Näiden proteiinien tutkimuksissa tarvittavaa terminologiaa

https://www.sciencedirect.com/science/article/abs/pii/S1043661819309491Abstract

Kelch-like gene family members (KLHLs) encode proteins with a bric-a-brac, tramtrack, broad complex (BTB)/poxvirus and zinc finger (POZ) domain, a BACK domain, and six Kelch motifs, which frequently interact with Cullin3 to form E3 ligase complexes that mediate the ubiquitination of substrate proteins. In recent years, studies have revealed that mutations and abnormal expression of KLHLs are closely related to the pathogenesis of various human diseases. Increasing evidence has shown that Kelch-like protein family members (KLHLs) exert important biological functions through the ubiquitination of specific substrates. This review provides an overview of the identified substrates of different KLHLs, summarizes the current knowledge of KLHLs and discusses the biological functions of KLHLs in different diseases.

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Abbreviations

KLHLs Kelch-like gene family members

BTBbric-a-brac

tramtrackbroad complex

POZ, poxvirus and zinc finger

KLHLs, Kelch-like protein family members

Ub. ubiquitin

K. lysine

NF-κB, nuclear factor kappa-B

KLHL. Kelch-like

Cul3, Cullin3

ZnF, zinc finger

NM, nemaline myopathy

KEAP1, Kelch-like ECH-associated protein 1,(KLHL19)

ROS, reactive oxygen species

Nrf2, nuclear factor erythroid 2-related factor

NQO1, NAD (P) H quinone oxidoreductase 1

HMOX1, heme oxygenase 1

GCL, glutamate-cysteine ligase

GSTs, glutathione S transferases

IVR, intervening region

ARE, antioxidant response element

DAPK, death-associated protein kinase

ULK1, unc-51 like autophagy activating kinase 1

VPS34, phosphatidylinositol 3-kinase VPS34

PML, promyelocytic leukaemia

APL, acute promyelocytic leukaemia

TGN, trans-Golgi network

NPCD, neuronal pentraxin with chromo domain

WNK4, with-no-lysine kinase 4

WNK, with-no-lysine kinase

NCC, NaCl cotransporter

PHAII, pseudohypoaldosteronism type II

NEB, nebulin

LMOD3, leiomodin 3

ABC-DLBCL, activated B cell-like diffuse large B-cell lymphoma

CDE, constitutive decay element

CDK2, cyclin-dependent kinase 2

AML, acute myeloid leukaemia

KLHL24-ΔN28, KLHL24 protein lacking the initial 28 amino acids

DGR, double glycine repeat or Kelch repeat

HIF-1, hypoxia inducible factor-1

PLK1, Polo-like kinase 1

DEPDC5, DEP domain containing 5

mTORC1, mammalian target of rapamycin 1

ENC1, ectodermal-neural cortex 1

HCL,  hairy cell leukaemia

TUT1, terminal uridylyl transferase 1

adRP,  autosomal-dominant form of retinitis pigmentosa

GAN, gigaxonin, (KLHL16)

PBC, primary biliary cholangitis

SjS, Sjögren’s syndrome

COPD, chronic obstructive pulmonary disease

DMF, dimethyl fumarate

MS, multiple sclerosis

PPIs, protein-protein interactions

C/EBPβ

CCAAT-enhancer binding protein β,
C/EBPδ, CCAAT-enhancer binding protein δ

dBruce, BIR repeat containing ubiquitin-conjugating enzyme(giant inhibitor of apoptosis-like protein)

SEC31, secretory 31

KHSRP, KH-type splicing regulatory protein or FBP2

IRES, internal ribosome entry sites

DSB, DNA double-strand breaks

PP2A, protein phosphatase 2A

MAP1B-LC, the light chain of microtubule-associated protein 1B

ATG16L1, autophagy related 16 like 1

MAP8, microtubule-associated protein

GFAP, glial-specific intermediate filament protein

IFs, intermediate filaments

TBCB, tubulin folding cofactor B

IKKβ, IκB kinase β

p62, sequestosome 1

Bcl-2, B cell leukaemia/lymphoma 2

PGAM5, phosphoglycerate mutase family 5

PDZ-RhoGEF, PDZ-Rho guanine nucleotide exchange factor

EB, end binding proteins

ACLY, ATP-citrate lyase

4E-BPs, 4E-binding proteins

FlnC, Filamin-C

NRAP, nebulin-related anchoring protein

? not clear

N/A, non-amplified

DLBCL, diffuse large B-cell lymphoma

CLL, chronic lymphocytic leukaemia

MZL, marginal zone lymphoma

MM, multiple myeloma

GC, gastric cancer

ALL, acute lymphoblastic B cell leukaemia

*protein stop codon

HCC, human hepatocellular carcinoma

CCA, cholangiocarcinoma

SCA8, spinocerebellar ataxia type 8

C/CISS1, crisponi/cold-induced sweating syndrome type 1

HCM, hypertrophic cardiomyopathy

ins, a single amino acid insertion

Thrfs*, frameshift change

Chemical compounds studied in this article

Nutlin-3A (PubChem CID: 11433190)

Dimethyl fumarate (PubChem CID: 637568)

ML334/LH601A (PubChem CID: 56840728)

Keywords, Avainsanoja

KLHLs Kelch tyyppiset proteiinit ( adaptoriproteiineja)

E3 ligase,  E3 ligaasi

Ubiquitination, ubikitinaatio

Substrate, substraatti

Cancer, syöpä

Hereditary diseases, perinnöllisiä tauteja

Chronic diseases, kroonisia tauteja