scholarly journals Identification of a PEST Sequence in Vertebrate KIR2.1 That Modifies Rectification

2019 ◽  
Vol 10 ◽  
Author(s):  
Muge Qile ◽  
Yuan Ji ◽  
Marien J. C. Houtman ◽  
Marlieke Veldhuis ◽  
Fee Romunde ◽  
...  
Keyword(s):  
2014 ◽  
Vol 106 (2) ◽  
pp. 660a
Author(s):  
Holly E. Dembinski ◽  
Elizabeth A. Komives

2002 ◽  
Vol 361 (3) ◽  
pp. 489-496 ◽  
Author(s):  
Jennifer I. SEMPLE ◽  
Stephanie E. BROWN ◽  
Christopher M. SANDERSON ◽  
R. Duncan CAMPBELL

The inhibitory κB (IκB)-like (IκBL) gene is located within the Class III region of the MHC on human chromosome 6. Previous analysis of the predicted amino acid sequence of the human IκBL protein revealed three putative functional domains; 2–3 ankyrin repeat sequences, which are similar to the second and third ankyrin repeats of the nuclear factor κB (NF-κB) protein; three PEST sequence motifs (a sequence that is rich in proline, serine, aspartic acid and threonine residues), which are also found in other IκB family members; and a C-terminal leucine zipper-like motif. In the present study we have identified a novel bipartite motif, which is required for nuclear localization of the IκBL protein. Analyses of IκBL-specific transcripts revealed the existence of a widely expressed spliced variant form of IκBL (IκBLsv1), which lacks the amino acid sequence GELEDEWQEVMGRFE (where single-letter amino-acid notation has been used). Interestingly, translation of IκBL mRNA in vivo was found to initiate predominantly from the second available methionine, thereby resulting in the disruption of the predicted N-terminal PEST sequence. Also, transient expression of T7 epitope-tagged IκBL and IκBLsv1 proteins in mammalian cells showed that both proteins were targeted to the nucleus, where they accumulate in nuclear speckles. To define the protein domains required for nuclear import and subnuclear localization, a complementary set of deletion mutants and enhanced green fluorescent protein—IκBL domain fusions were expressed in mammalian cells. Data from these experiments show that a combination of the ankyrin-repeat region and an adjacent arginine-rich sequence are necessary and sufficient for both nuclear import and speckle localization.


2012 ◽  
Vol 13 (1) ◽  
pp. 20 ◽  
Author(s):  
Bin Li ◽  
Qingsong Hu ◽  
Ranjie Xu ◽  
Haigang Ren ◽  
Erkang Fei ◽  
...  
Keyword(s):  

2000 ◽  
Vol 275 (31) ◽  
pp. 23608-23614 ◽  
Author(s):  
Christelle Marchal ◽  
Rosine Haguenauer-Tsapis ◽  
Daniele Urban-Grimal

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0251279
Author(s):  
Juncal Garcia-Garcia ◽  
Katrine Stange Overå ◽  
Waqas Khan ◽  
Eva Sjøttem

TRIM32 is an E3 ligase implicated in diverse biological pathways and pathologies such as muscular dystrophy and cancer. TRIM32 are expressed both as full-length proteins, and as a truncated protein. The mechanisms for regulating these isoforms are poorly understood. Here we identify a PEST sequence in TRIM32 located in the unstructured region between the RING-BBox-CoiledCoil domains and the NHL repeats. The PEST sequence directs cleavage of TRIM32, generating a truncated protein similarly to the short isoform. We map three lysine residues that regulate PEST mediated cleavage and auto-ubiquitylation activity of TRIM32. Mimicking acetylation of lysine K247 completely inhibits TRIM32 cleavage, while the lysines K50 and K401 are implicated in auto-ubiquitylation activity. We show that the short isoform of TRIM32 is catalytic inactive, suggesting a dominant negative role. These findings uncover that TRIM32 is regulated by post-translational modifications of three lysine residues, and a conserved PEST sequence.


2009 ◽  
Vol 83 (22) ◽  
pp. 11819-11829 ◽  
Author(s):  
Charlotte Lepère-Douard ◽  
Maud Trotard ◽  
Jacques Le Seyec ◽  
Philippe Gripon

ABSTRACT The early steps of the hepatitis B virus (HBV) life cycle are still poorly understood. Indeed, neither the virus receptor at the cell surface nor the mechanism by which nucleocapsids are delivered to the cytosol of infected cells has been identified. Extensive mutagenesis studies in pre-S1, pre-S2, and most of the S domain of envelope proteins revealed the presence of two regions essential for HBV infectivity: the 77 first residues of the pre-S1 domain and a conformational motif in the antigenic loop of the S domain. In addition, at the N-terminal extremity of the S domain, a putative fusion peptide, partially overlapping the first transmembrane (TM1) domain and preceded by a PEST sequence likely containing several proteolytic cleavage sites, was identified. Since no mutational analysis of these two motifs potentially implicated in the fusion process was performed, we decided to investigate the ability of viruses bearing contiguous deletions or substitutions in the putative fusion peptide and PEST sequence to infect HepaRG cells. By introducing the mutations either in the L and M proteins or in the S protein, we demonstrated the following: (i) that in the TM1 domain of the L protein, three hydrophobic clusters of four residues were necessary for infectivity; (ii) that the same clusters were critical for S protein expression; and, finally, (iii) that the PEST sequence was dispensable for both assembly and infection processes.


Sign in / Sign up

Export Citation Format

Share Document