Btbd6-dependent Plzf recruitment to Cul3 E3 ligase complexes through BTB domain heterodimerization

AbstractThe Cul3 adaptor Btbd6 plays crucial roles in neural development by driving the ubiquitin-dependent degradation of promyelocytic zinc finger transcription factor (Plzf). Btbd6 has conserved motifs, BTB-BACK-PHR, and by analogy with other BTB-BACK adaptors, might be expected to bind to Cul3 through the BTB-BACK domain, and to substrate through the PHR domain. However, we now present a mode of adaptor-substrate interaction through heterodimerisation between the normally homodimeric BTB domains of Btbd6 and Plzf. This heterodimerization appears to occur through monomer exchange that is detected only at or near physiological concentrations. The Btbd6-Plzf heterodimer thus formed assembles into a ternary complex with Cul3. In addition we show that the BTB and PHR domains of Btbd6 promote localisation in the nucleus and that the BACK domain contains a nuclear export signal. Our findings support a model whereby Btbd6 moves into and out of the nucleus, iteratively ‘sweeping’ Plzf into the cytoplasm and enabling complex formation with Cul3 that presents Plzf for ubiquitination.HighlightsA general mechanism for recruitment of BTB domain-containing substrates by BTBdomain adaptors for the Cul3 E3 ligase complexNuclear export of the Plzf/Btbd6 complex mediated by a NES within the Btbd6 BACK domainCul3-dependent Plzf ubiquitylation through heterodimerisation of BTB domains on adaptor and substrate by monomer exchang

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Identification and characterization of a CRM1/XPO1-dependent nuclear export signal in the human androgen receptor

Endocrine Abstracts ◽

10.1530/endoabs.42.p24 ◽

2016 ◽

Author(s):

Stefanie V Schutz ◽

Axel Merseburger ◽

Anca Azoitei ◽

Marcus V Cronauer

Keyword(s):

Androgen Receptor ◽

Nuclear Export ◽

Nuclear Export Signal ◽

Export Signal ◽

Identification And Characterization ◽

Human Androgen Receptor

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The Structure of BRMS1 Nuclear Export Signal and SNX6 Interacting Region Reveals a Hexamer Formed by Antiparallel Coiled Coils

Journal of Molecular Biology ◽

10.1016/j.jmb.2011.07.006 ◽

2011 ◽

Vol 411 (5) ◽

pp. 1114-1127 ◽

Cited By ~ 9

Author(s):

Mercedes Spínola-Amilibia ◽

José Rivera ◽

Miguel Ortiz-Lombardía ◽

Antonio Romero ◽

José L. Neira ◽

...

Keyword(s):

Nuclear Export ◽

Nuclear Export Signal ◽

Coiled Coils ◽

Export Signal

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Nuclear Export of L-Periaxin, Mediated by Its Nuclear Export Signal in the PDZ Domain

PLoS ONE ◽

10.1371/journal.pone.0091953 ◽

2014 ◽

Vol 9 (3) ◽

pp. e91953 ◽

Cited By ~ 8

Author(s):

Yawei Shi ◽

Lei Zhang ◽

Ting Yang

Keyword(s):

Nuclear Export ◽

Pdz Domain ◽

Nuclear Export Signal ◽

Export Signal

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Properties of Two EBV Mta Nuclear Export Signal Sequences

Virology ◽

10.1006/viro.2001.1057 ◽

2001 ◽

Vol 288 (1) ◽

pp. 119-128 ◽

Cited By ~ 22

Author(s):

Lin Chen ◽

Gangling Liao ◽

Masahiro Fujimuro ◽

O.John Semmes ◽

S.Diane Hayward

Keyword(s):

Nuclear Export ◽

Nuclear Export Signal ◽

Signal Sequences ◽

Export Signal

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OsWRKY62 and OsWRKY76 interact with Importin α1s for Negative Regulation of Defensive Responses in Nucleus

10.21203/rs.3.rs-636974/v1 ◽

2021 ◽

Author(s):

Xiaohui Xu ◽

Han Wang ◽

Jiqin Liu ◽

Shuying Han ◽

Miaomiao Lin ◽

...

Keyword(s):

Amino Acids ◽

Nuclear Localization ◽

Nuclear Export ◽

Nuclear Translocation ◽

Nuclear Export Signal ◽

Defense Responses ◽

Nuclear Localization Signals ◽

Defensive Responses ◽

Export Signal ◽

Positively Charged

Abstract Background: OsWRKY62 and OsWRKY76, two close members of WRKY transcription factors, function together as transcriptional repressors. OsWRKY62 is predominantly localized in the cytosol. What are the regulatory factors for OsWRKY62 nuclear translocation?Results: In this study, we characterized they interacted with rice importin, OsIMα1a and OsIMα1b, for nuclear translocation. Chimeric OsWRKY62.1-GFP, which is predominantly localized in the cytoplasm, was translocated to the nucleus of Nicotiana benthamiana leaf cells in the presence of OsIMα1a or OsIMαDIBB1a lacking the auto-inhibitory importin β-binding domain. OsIMαDIBB1a interacted with the WRKY domain of OsWRKY62.1, which has specific bipartite positively charged concatenated amino acids functioning as a nuclear localization signal. Similarly, we found that OsIMαDIBB1a interacted with the AvrPib effector of rice blast fungus Magnaporthe oryzae, which contains a scattered distribution of positively charged amino acids. Furthermore, we identified a nuclear export signal in OsWRKY62.1 that inhibited nuclear transportation. Overexpression of OsIMα1a or OsIMα1b enhanced resistance to M. oryzae, whereas knockout mutants decreased resistance to the pathogen. However, overexpressing both OsIMα1a and OsWRKY62.1 were slightly more susceptible to M. oryzae than OsWRKY62.1 alone. Ectopic overexpression of OsWRKY62.1 with an extra nuclear export signal compromised the enhanced susceptibility of OsWRKY62.1 to M. oryzae.Conclusion: These results indicated that OsWRKY62 localization is a consequence of competition binding between rice importins and exportins. OsWRKY62, OsWRKY76, and AvrPib effector translocate to nucleus in association with importin α1s through new types of nuclear localization signals for negatively regulating defense responses.

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Structural determinants of nuclear export signal orientation in binding to exportin CRM1

eLife ◽

10.7554/elife.10034 ◽

2015 ◽

Vol 4 ◽

Cited By ~ 44

Author(s):

Ho Yee Joyce Fung ◽

Szu-Chin Fu ◽

Chad A Brautigam ◽

Yuh Min Chook

Keyword(s):

Crystal Structures ◽

Nuclear Export ◽

Chromosome Region ◽

Nuclear Export Signal ◽

Opposite Orientation ◽

Structural Determinants ◽

Large Expansion ◽

Export Signal

The Chromosome Region of Maintenance 1 (CRM1) protein mediates nuclear export of hundreds of proteins through recognition of their nuclear export signals (NESs), which are highly variable in sequence and structure. The plasticity of the CRM1-NES interaction is not well understood, as there are many NES sequences that seem incompatible with structures of the NES-bound CRM1 groove. Crystal structures of CRM1 bound to two different NESs with unusual sequences showed the NES peptides binding the CRM1 groove in the opposite orientation (minus) to that of previously studied NESs (plus). Comparison of minus and plus NESs identified structural and sequence determinants for NES orientation. The binding of NESs to CRM1 in both orientations results in a large expansion in NES consensus patterns and therefore a corresponding expansion of potential NESs in the proteome.

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Regulation of intracellular dynamics of Smad4 by its leucine‐rich nuclear export signal

EMBO Reports ◽

10.1093/embo-reports/kvd029 ◽

2000 ◽

Vol 1 (2) ◽

pp. 176-182 ◽

Cited By ~ 94

Author(s):

Mina Watanabe ◽

Norihisa Masuyama ◽

Makoto Fukuda ◽

Eisuke Nishida

Keyword(s):

Nuclear Export ◽

Nuclear Export Signal ◽

Export Signal

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p65 controls NF-κB activity by regulating cellular localization of IκBβ

Biochemical Journal ◽

10.1042/bj20101220 ◽

2011 ◽

Vol 434 (2) ◽

pp. 253-263 ◽

Cited By ~ 11

Author(s):

Taras Valovka ◽

Michael O. Hottiger

Keyword(s):

Dna Binding ◽

Nuclear Export ◽

Cellular Localization ◽

Nuclear Export Signal ◽

Nuclear Factor Κb ◽

Binding Activity ◽

Cellular Processes ◽

Dna Binding Activity ◽

Localization Signal ◽

Export Signal

NF-κB (nuclear factor κB) controls diverse cellular processes and is frequently misregulated in chronic immune diseases or cancer. The activity of NF-κB is regulated by IκB (inhibitory κB) proteins which control nuclear–cytoplasmic shuttling and DNA binding of NF-κB. In the present paper, we describe a novel role for p65 as a critical regulator of the cellular localization and functions of NF-κB and its inhibitor IκBβ. In genetically modified p65−/− cells, the localization of ectopic p65 is not solely regulated by IκBα, but is largely dependent on the NLS (nuclear localization signal) and the NES (nuclear export signal) of p65. Furthermore, unlike IκBα, IκBβ does not contribute to the nuclear export of p65. In fact, the cellular localization and degradation of IκBβ is controlled by the p65-specific NLS and NES. The results of our present study also reveal that, in addition to stimulus-induced redistribution of NF-κB, changes in the constitutive localization of p65 and IκBβ specifically modulate activation of inflammatory genes. This is a consequence of differences in the DNA-binding activity and signal responsiveness between the nuclear and cytoplasmic NF-κB–IκBβ complexes. Taken together, the findings of the present study indicate that the p65 subunit controls transcriptional competence of NF-κB by regulating the NF-κB/IκBβ pathway.

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