Nucleolar localization of an isoform of the IGF-I precursor

Tan, Daniel S.W.; Cook, Alexandra; Chew, Shern L.

doi:10.1186/1471-2121-3-17

Cited by 42 publications

(25 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, we speculate that the MGF peptide is directly involved in transcriptional processes. Similar localizations of MGF have been described in experiments in HeLa cells using IGF exons tagged with green fluorescent protein [59]. Furthermore, a clear nuclear localization signal “RRRK” within the Ec peptide has been observed when using the PROST II program for sequence comparison [60].…”

Section: Discussionsupporting

confidence: 74%

See 1 more Smart Citation

Insulin-Like Growth Factor I (IGF-1) Ec/Mechano Growth Factor – A Splice Variant of IGF-1 within the Growth Plate

et al. 2013

View full text Add to dashboard Cite

Human insulin-like growth factor 1 Ec (IGF-1Ec), also called mechano growth factor (MGF), is a splice variant of insulin-like growth factor 1 (IGF-1), which has been shown in vitro as well as in vivo to induce growth and hypertrophy in mechanically stimulated or damaged muscle. Growth, hypertrophy and responses to mechanical stimulation are important reactions of cartilaginous tissues, especially those in growth plates. Therefore, we wanted to ascertain if MGF is expressed in growth plate cartilage and if it influences proliferation of chondrocytes, as it does in musculoskeletal tissues. MGF expression was analyzed in growth plate and control tissue samples from piglets aged 3 to 6 weeks. Furthermore, growth plate chondrocyte cell culture was used to evaluate the effects of the MGF peptide on proliferation. We showed that MGF is expressed in considerable amounts in the tissues evaluated. We found the MGF peptide to be primarily located in the cytoplasm, and in some instances, it was also found in the nucleus of the cells. Addition of MGF peptides was not associated with growth plate chondrocyte proliferation.

show abstract

Section: Discussionsupporting

confidence: 74%

“…MGF can be regarded as an autocrine factor with an extremely short half-life outside the nuclear environment [19], [27], [59]. We favour the idea that MGF is an intracellular peptide with a clear nuclear localization signal, and probably features a function in the transcriptional process.…”

Section: Discussionmentioning

confidence: 81%

Insulin-Like Growth Factor I (IGF-1) Ec/Mechano Growth Factor – A Splice Variant of IGF-1 within the Growth Plate

et al. 2013

View full text Add to dashboard Cite

show abstract

“…By looking for sequential similarities between the hLa-NoLS described here and other published sequences mediating nucleolar localization of different human proteins (45)(46)(47)(48)(49)(50)(51)(75)(76)(77)(78), we aligned those sequences with the hLa-NoLS (Fig. 4C).…”

Section: Discussionmentioning

confidence: 99%

Nuclear Trafficking of La Protein Depends on a Newly Identified Nucleolar Localization Signal and the Ability to Bind RNA

Horke

Reumann

Schweizer

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

Here we provide evidence for an interaction-dependent subnuclear trafficking of the human La (hLa) protein, known as transient interaction partner of a variety of RNAs. Among these, precursor transcripts of certain RNAs are located in the nucleoplasm or nucleolus. Here we examined which functional domains of hLa are involved in its nuclear trafficking. By using green fluorescent-hLa fusion proteins, we discovered a nucleolar localization signal and demonstrated its functionality in a heterologous context. In addition, we revealed that the RRM2 motif of hLa is essential both for its RNA binding competence in vitro and in vivo and its exit from the nucleolus. Our data imply that hLa traffics between different subnuclear compartments, which depend decisively on a functional nucleolar localization signal as well as on RNA binding. Directed trafficking of hLa is fully consistent with its function in the maturation of precursor RNAs located in different subnuclear compartments.The human La protein (hLa) 1 is a 47-kDa phosphoprotein predominantly localized in the nucleus. It was first discovered as an autoantigen recognized by antibodies present in the sera of patients suffering from systemic lupus erythematosus and Sjogren's syndrome (1, 2). The La protein is a member of a large group of RNA-binding proteins containing RNA recognition motifs (RRMs) (3-7) and interacts with a variety of small RNAs (for reviews see Refs. 8 -10). The La protein is implicated in several aspects of the RNA metabolism, including processing of precursors of tRNAs, U3 snoRNA, U1 RNA, U6 snRNA (11)(12)(13)(14)(15)(16)(17)(18)(19)(20), and stabilization of viral (21-23) as well as cellular RNAs (24). In the cytoplasm, La has been implicated in the translational control of viral (25-27) and cellular RNAs (28 -30).The human La protein contains a nuclear localization sequence at the very C-terminal end, and the staining for endogenous La as well as the distribution of GFP-tagged La reveal a predominantly diffuse nuclear staining, although this may appear different under certain conditions or treatments (31-33). Subcellular distribution of human and yeast La was assumed to be independent of phosphorylation (34, 35); however, recent studies (36, 37) revealed that phosphorylation at Ser-366 may well influence subcellular localization of La. A regulated, nonhomogeneous nuclear distribution of La may also be predicted from the distinct nuclear distribution of its various RNA interaction partners. For instance, pre-tRNAs are most likely synthesized in the nucleoplasm (38) but are processed, at least in part, in the nucleolus (39, 40), whereas in yeast the La-associated precursor of U3 snoRNA is probably processed in the nucleolar body and nucleolus (20). Nevertheless, interactions with precursor RNAs in different nuclear compartments implicate a highly dynamic and regulated nuclear distribution of La. Although a nucleolar localization of La has been reported (for review see Ref. 9), the hLa protein was not identified among the recently resolved protein ...

show abstract

“…Post-translational processing has been examined in both 293 and Chinese hamster ovary cell lines (Duguay 1999). The processing seems to occur via a constitutive secretory pathway, similarly directed by class 1 and 2 signal peptides (Tan et al 2002). The peptide precursor (proIGF-I) contains the E peptide in addition to the domains in the mature peptide.…”

Section: Peptide Cleavagementioning

confidence: 99%

“…A recent study has provided evidence that human proIGF-IB might traffic differently. Tan et al (2002) constructed chimeric IGF-I precursors inserting green fluorescent protein (GFP) between the signal and mature peptide domains, and examined where the products went in cultured HeLa cells. When the chimeras contained exon 5 and not exon 6, GFP fluorescence was concentrated in the nucleolus.…”

Section: Potential Functions Of Igf-i E Peptidesmentioning

confidence: 99%

The ABCs of IGF-I isoforms: impact on muscle hypertrophy and implications for repair

Barton

2006

Appl. Physiol. Nutr. Metab.

119

114

View full text Add to dashboard Cite

Insulin-like growth factor I (IGF-I) plays a critical role in the growth and development of many tissues in the body. It is a key regulator of skeletal muscle development, and continues to enhance the ability for muscle to grow and undergo repair throughout life. Although the focus of research has been on the molecular actions and physiological impact of IGF-I, there has also been a growing undercurrent of studies geared toward the characterization of additional potentially active peptides produced by the igf1 gene. Alternative splicing of the gene results in multiple isoforms that retain the identical sequence for mature IGF-I, but also give rise to divergent C-terminal peptides. The peptides might modulate the actions, stability, or bioavailability of IGF-I, or they might have independent activity. These possibilities have gained the attention of the skeletal muscle field, where novel actions of IGF-I could have significant impact on muscle mass, strength, and repair.

show abstract

Nucleolar localization of an isoform of the IGF-I precursor

Cited by 42 publications

References 16 publications

Insulin-Like Growth Factor I (IGF-1) Ec/Mechano Growth Factor – A Splice Variant of IGF-1 within the Growth Plate

Insulin-Like Growth Factor I (IGF-1) Ec/Mechano Growth Factor – A Splice Variant of IGF-1 within the Growth Plate

Nuclear Trafficking of La Protein Depends on a Newly Identified Nucleolar Localization Signal and the Ability to Bind RNA

The ABCs of IGF-I isoforms: impact on muscle hypertrophy and implications for repair

Contact Info

Product

Resources

About