Abstract
We have previously identified and characterized human KLHDC2/HCLP-1, a kelch repeat protein that interacts with and inhibits transcription factor LZIP. In this study, we identified and characterized a paralog of KLHDC2 called KLHDC1. KLHDC1 and KLHDC2 share about 50% identity at the level of amino acid sequence and both gene loci localize to human chromosome 14q21.3. This cluster of KLHDC1 and KLHDC2 genes is highly conserved in vertebrates ranging from pufferfish to human. Both genes are expressed highly in skeletal muscle, but weakly in various other tissues. While KLHDC2 was predominantly found in the nucleus, KLHDC1 is a cytoplasmic protein. Neither KLHDC1 nor KLHDC2 binds to actin. In addition, KLHDC1 was unable to inhibit LZIP/CREB3-mediated transcriptional activation. Thus, KLHDC1 and KLHDC2 have differential localization and activity in cultured mammalian cells.
Similar content being viewed by others
Abbreviations
- BD:
-
Gal4 DNA binding domain
- HCA33:
-
hepatocellular carcinoma-associated antigen 33
- HCF:
-
host cell factor 1
- HCLP:
-
HCF-like protein
- HUGO:
-
the human genome organization
- KLHDC:
-
kelch domain containing protein
References
Xue F, Cooley L: Kelch encodes a component of intercellular bridges in Drosophila egg chambers Cell 72:681–693, 1993
Prag S, Adams JC: Molecular phylogeny of the kelch-repeat superfamily reveals an expansion of BTB/kelch proteins in animals BMC Bioinformatics 4:42, 2003
Ito N, Phillips SEV, Yadav KDS, Knowles PF: Crystal structure of a free radical enzyme, galactose oxidase J Mol Biol 238:794–814, 1994
Robinson DN, Cooley L: Drosophila kelch is an oligomeric ring canal actin organiser J Cell Biol 138:799–810, 1997
Adams JC, Kelso R, Cooley L: The kelch repeat superfamily: propellers of cell function Trends Cell Biol 10, 17–24, 2000
Wilson AC, LaMarco K, Peterson MG, Herr W: The VP16 accessory protein HCF is a family of polypeptides processed from a large precursor protein Cell 74:115–125, 1993
Kristie TM, Sharp PA: Purification of the cellular C1 factor required for the stable recognition of the Oct-1 homeodomain by the herpes simplex virus α-transinduction factor (VP16) J Biol Chem 268:6525–6534, 1993
Lu R, Yang P, O’Hare P, Misra V: Luman, a new member of the CREB/ATF family, binds to herpes simplex virus VP16-associated host cell factor Mol Cell Biol 17:5117–5126, 1997
Freiman RN, Herr W: Viral mimicry: common mode of association with HCF by VP16 and the cellular protein LZIP Genes Dev 11, 3122–3127, 1997
Vogel JL, Kristie TM: The novel coactivator C1 (HCF) coordinates multiprotein enhancer formation and mediates transcription activation by GABP EMBO J 19, 683–669, 2000
Wilson AC, Boutros M, Johnson KM, Herr W: HCF-1 amino- and carboxyterminal subunit association through two separate sets of interaction modules: involvement of fibronectin type 3 repeats Mol Cell Biol 20:6721–6730, 2000
Wysocka J, Myers MP, Laherty CD, Eisenman RN, Herr W: Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3-K4 methyltransferase are tethered together selectively by the cell-proliferation factor HCF-1 Genes Dev 17:896–911, 2003
Wysocka J, Reilly PT, Herr W: Loss of HCF-1-chromatin association precedes temperature-induced growth arrest of tsBN67 cells Mol Cell Biol 21:3820–3829, 2001
Julien E, Herr W: A switch in mitotic histone H4 lysine 20 methylation status is linked to M phase defects upon loss of HCF-1 Mol Cell 14:713–725, 2004
Zhou HJ, Wong CM, Chen JH, Qiang BQ, Yuan JG, Jin DY: Inhibition of LZIP-mediated transcription through direct interaction with a novel host cell factor-like protein J Biol Chem 276:28933–28938, 2001
Diaz E, Schimmoller F, Pfeffer SR: A novel Rab9 effector required for endosome-to-TGN transport J Cell Biol 138:283–290, 1997
Jin DY, Wang HL, Zhou Y, Chun ACS, Kibler KV, Hou YD, Kung H, Jeang KT: Hepatitis C virus core protein-induced loss of LZIP function correlates with cellular transformation EMBO J 19:729–740, 2000
Chin KT, Zhou HJ, Wong CM, Lee JMF, Chan CP, Qiang BQ, Yuan JG, Ng IOL, Jin DY: The liver-enriched transcription factor CREB-H is a growth suppressor protein underexpressed in hepatocellular carcinoma Nucl Acids Res 33:1859–1873, 2005
apRhys CMJ, Ciufo DM, O’Neill EA, Kelly TJ, Hayward GS: Overlapping octamer and TAATGARAT motifs in the VF65-response elements in herpes simplex virus immediate-early promoters represent independent binding sites for cellular nuclear factor III J Virol 63:2798–2812, 1989
Zhou Y, Kok KH, Chun ACS, Wong CM, Wu HW, Lin MCM, Fung PCW, Kung H, Jin DY: Mouse peroxiredoxin V is a thioredoxin peroxidase that inhibits p53-induced apoptosis Biochem Biophys Res Commun 268:921–927, 2000
Zhou Y, Ching YP, Ng RWM, Jin DY: Differential expression, localization and activity of two alternatively spliced isoforms of human APC regulator CDH1 Biochem J 374:349–358, 2003
Siu YT, Chin KT, Siu KL, Choy EYW, Jeang KT, Jin DY: TORC1 and TORC2 coactivators are required for Tax activation of the human T-cell leukemia virus type 1 long terminal repeats J Virol 80:7052–7059, 2006
Zhou Y, Ching YP, Chun ACS, Jin DY: Nuclear localization of the cell cycle regulator CDH1 and its regulation by phosphorylation J Biol Chem 278:12530–12536, 2003
Ching YP, Chan SF, Jeang KT, Jin DY: Retroviral oncoprotein Tax targets coiled-coil centrosomal protein TAX1BP2 to induce centrosome overduplication Nat Cell Biol 8:717–724, 2006
Chen JH, Luo WQ, Zhou Y, Tan XY, Li GT, Huang XW, Zhou HJ, Li WJ, Yuan JG, Qiang BQ: cDNA cloning and expression in E. coli of a human new gene HCL Prog Nat Sci 10:1001–1005, 2000
Sadowski I, Ma J, Triezenberg SJ, Ptashne M: GAL4-VP16 is an unusually potent transcriptional activator Nature 335:563–564, 1988
Baichwal VR, Park A, Tjian R: v-Src and EJ Ras alleviate repression of c-Jun by a cell-specific inhibitor Nature 352:165–168, 1991
Jin DY, Spencer F, Jeang KT: Human T cell leukemia virus type 1 oncoprotein Tax targets the human mitotic checkpoint protein MAD1 Cell 93:81–91, 1998
Yedowitz JC, Kotsakis A, Schlegel EF, Blaho JA: Nuclear localizations of the herpes simplex virus type 1 tegument proteins VP13/14, vhs, and VP16 precede VP22-dependent microtubule reorganization and VP22 nuclear import J Virol 79:4730–4743, 2005
Chida K, Nagamori S, Kuroki T: Nuclear translocation of Fos is stimulated by interaction with Jun through the leucine zipper Cell Mol Life Sci 55:297–302, 1999
Gettemans J, Meerschaert K, Vandekerckhove J, De Corte V: A kelch β propeller featuring as a Gβ structural mimic: reinventing the wheel? Sci. STKE 191: PE27, 2003
Vogel JL, Kristie TM: Autocatalytic proteolysis of the transcription factor coactivator Cl (HCF): a potential role for proteolytic regulation of coactivator function Proc Natl Acad Sci USA 97:9425–9430, 2000
Julien E, Herr W: Proteolytic processing is necessary to separate and ensure proper cell growth and cytokinesis functions of HCF-1 EMBO J 22, 2360–2369, 2003
Johnson KM, Mahajan SS, Wilson AC: Herpes simplex virus transactivator VP16 discriminates between HCF-1 and a novel family member, HCF-2 J Virol 73:3930–3940, 1999
Lee S, Herr W: Stabilization but not the transcriptional activity of herpes simplex virus VP16-induced complexes is evolutionarily conserved among HCF family members J Virol 75:12402–12411, 2001
Raggo C, Rapin N, Stirling J, Gobeil P, Smith-Windsor E, O’Hare P, Misra V: Luman, the cellular counterpart of herpes simplex virus VP16, is processed by regulated intramembrane proteolysis Mol Cell Biol 22:5639–5649, 2002
Kondo S, Murakami T, Tatsumi K, Ogata M, Kanemoto S, Otori K, Iseki K, Wanaka A, Imaizumi K: OASIS, a CREB/ATF-family member, modulates UPR signalling in astrocytes Nat Cell Biol 7:186–194, 2005
Acknowledgments
We thank G.S. Hayward for gift of plasmid and A.C.S. Chun for critical reading of the manuscript. D.-Y. Jin is a Leukemia and Lymphoma Society Scholar. This work was supported by a grant to D.-Y. Jin from the Hong Kong Research Grants Council (Project HKU 7294/02M).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Chin, KT., Xu, HT., Ching, YP. et al. Differential subcellular localization and activity of kelch repeat proteins KLHDC1 and KLHDC2. Mol Cell Biochem 296, 109–119 (2007). https://doi.org/10.1007/s11010-006-9304-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11010-006-9304-6