La autoantigen enhances translation of BiP mRNA

Kim, Yoon Ki; Back, Sung Hoon; Rho, Jungmin; Lee, Song Hee; Jang, Sung Key

doi:10.1093/nar/29.24.5009

Cited by 85 publications

(91 citation statements)

References 73 publications

(89 reference statements)

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“…Several reports suggest a role of La in IRESdependent translation (Belsham et al, 1995;Ali et al, 2000;Holcik and Korneluk, 2000;Kim et al, 2001). Hence, we tested whether La regulates the CCND1 IRES element (Shi et al, 2005;Jo et al, 2008).…”

Section: La Associates With Ccnd1 Mrnamentioning

confidence: 99%

The RNA-binding protein La contributes to cell proliferation and CCND1 expression

et al. 2010

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The La protein is an essential RNA-binding protein implicated in different aspects of RNA metabolism. Herein, we report that small interfering (siRNA)-mediated La depletion reduces cell proliferation of different cell lines concomitant with a reduction in cyclin D1 (CCND1) protein. To exclude off-target effects we demonstrate that exogenous La expression in La-depleted cells restores cell proliferation and CCND1 protein levels. In contrast, proliferation of immortalized CCND1 knockout cells is not affected by La depletion, supporting a functional coherence between La, CCND1 and proliferation. Furthermore, we document by reversible in vivo crosslinking and ribonucleoprotein (RNP) immunoprecipitation an association of the La protein with CCND1 messengerRNA and that CCND1 internal ribosome entry site (IRES)-dependent translation is modulated by La protein level within the cell. In addition, we show elevated La protein expression in cervical cancer tissue and its correlation with aberrant CCND1 protein levels in cervical tumor tissue lysates. In conclusion, this study establishes a role of La in cell proliferation and CCND1 expression and demonstrates for the first time an overexpression of the RNA-binding protein La in solid tumors.

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Section: La Associates With Ccnd1 Mrnamentioning

confidence: 99%

The RNA-binding protein La contributes to cell proliferation and CCND1 expression

et al. 2010

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“…53 Bip IRES function is, however, increased in the presence of the La autoantigen. 54 The mechanism by which PTB regulates IRES recruitment is unknown; however, one model is that PTB binds to the cellular IRES and then directly interacts with the ribosome. Alternatively, PTB could indirectly recruit the translation machinery via contacts with other factors such as: TLS/ FUS, which associates with the nuclear matrix, and also with PTB in the spliceosome; 55 unr, as mentioned above, which is required for PTB binding at the Apaf-1 IRES 45 and also, in conjunction with PTB, for maximal IRES activity in HRV; 56 Raver1, which is a hnRNP-like protein that forms complexes with microfilament attachment proteins vinculin and Figure 2 nPTB and unr act as RNA chaperones on the Apaf-1 IRES.…”

Section: Analysis Of Mrnas That Remain Polysomally Associated During mentioning

confidence: 99%

Internal ribosome entry segment-mediated translation during apoptosis: the role of IRES-trans-acting factors

et al. 2005

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During apoptosis, there is a reduction in translation initiation caused by caspase cleavage of several of the factors required for the cap-dependent scanning mechanism. Under these circumstances, many proteins that are required for apoptosis are instead translated by the alternative method of internal ribosome entry. This mechanism requires the formation of a complex RNA structural element and in the presence of internal ribosome entry segment (IRES)-trans-acting factors (ITAFs), the ribosome is recruited to the RNA. The interactions of several ITAFs with IRESs have been investigated in detail, and several mechanisms of action have been noted, including acting as chaperones, stabilising and remodelling the RNA structure. Structural remodelling by PTB in particular will be discussed, and how this protein is able to facilitate recruitment of the ribosome to several IRESs by causing previously occluded sites to become more accessible.

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“…La can shuttle between the nucleus and cytoplasm upon cellular stress (Baboonian et al, 1989;Bachmann et al, 1990). Cytoplasmic La promotes translation of a large variety of viral (Meerovitch et al, 1993;Chang et al, 1994) and cellular RNA (Kim et al, 2001;Holcik et al, 2003) through internal ribosome entry sites because of its modular structure (Trotta et al, 2003;Alfano et al, 2004;Dong et al, 2004). The fact that La is also able to facilitate translation of other mRNAs containing a 5 0 -UTR terminal oligopyrimidine element encoding ribosomal and translation relatedproteins (Crosio et al, 2000;Meyuhas, 2000;Cardinali et al, 2003) suggests a key role for La in mRNA translational regulation and makes La a potential candidate for the recruitment of oncogenic mRNAs to polysomes.…”

Section: Introductionmentioning

confidence: 99%

Akt phosphorylation of La regulates specific mRNA translation in glial progenitors

et al. 2008

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The Akt signaling pathway activity increases as normal tissue progresses to malignant transformation, and regulates the translation of specific messenger RNAs (mRNAs) through multiple mechanisms. We have identified one such mechanism of Akt-dependent translation control as involving the lupus autoantigen La. La is an RNA-associated protein that contains multiple trafficking elements to support the interaction with RNAs in different subcellular locations. We show here that the La protein is a direct target of the serine/threonine protein kinase Akt on threonine 301, and La nuclear export in mouse glial progenitors, as well as its association with polysomes is modulated by Akt activity. Using a functional approach to determine the network of genes affected by La in the cytoplasm by microarray analysis of polysome-bound mRNAs, we found that La binds 34% of the polysome bound mRNAs and regulates the expression of a specific pool of mRNAs under KRas/Akt activation. Therefore, La appears to be an important contributor to Aktmediated translational regulation of these transcripts in murine glial cells.

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La autoantigen enhances translation of BiP mRNA

Cited by 85 publications

References 73 publications

The RNA-binding protein La contributes to cell proliferation and CCND1 expression

The RNA-binding protein La contributes to cell proliferation and CCND1 expression

Internal ribosome entry segment-mediated translation during apoptosis: the role of IRES-trans-acting factors

Akt phosphorylation of La regulates specific mRNA translation in glial progenitors

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