Identification of chURP, a nuclear calmodulin‐binding protein related to hnRNP‐U

Lodge, Anthony P.; Walsh, Adrian A; McNamee, Christine J.; Moss, Darren M.

doi:10.1046/j.1432-1327.1999.00246.x

Cited by 5 publications

(3 citation statements)

References 76 publications

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“…Manp is a new member of the hnRNP family and is most probably the murine orthologue of chURP (30). Although the precise function of chURP has yet to be described, hnRNP-U/SAF-A plays an important role in regulating gene expression (31)(32)(33)40).…”

Section: Discussionmentioning

confidence: 99%

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Myeloid Leukemia Factor 1 Associates with a Novel Heterogeneous Nuclear Ribonucleoprotein U-like Molecule

Winteringham

Endersby²,

Kobelke

et al. 2006

Journal of Biological Chemistry

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Myeloid leukemia factor 1 (MLF1) is an oncoprotein associated with hemopoietic lineage commitment and acute myeloid leukemia. Here we show that Mlf1 associated with a novel binding partner, Mlf1-associated nuclear protein (Manp), a new heterogenous nuclear ribonucleoprotein (hnRNP) family member, related to hnRNP-U. Manp localized exclusively in the nucleus and could redirect Mlf1 from the cytoplasm into the nucleus. The nuclear content of Mlf1 was also regulated by 14-3-3 binding to a canonical 14-3-3 binding motif within the N terminus of Mlf1. Significantly Mlf1 contains a functional nuclear export signal and localized primarily to the nuclei of hemopoietic cells. Mlf1 was capable of binding DNA, and microarray analysis revealed that it affected the expression of several genes, including transcription factors. In summary, this study reveals that Mlf1 translocates between nucleus and cytoplasm, associates with a novel hnRNP, and influences gene expression. Myeloid leukemia factor 1 (MLF1)4 is a gene involved in hemopoietic lineage commitment and acute myeloid leukemia (1, 2). The gene was originally identified in a (3;5) translocation associated with acute myeloid leukemia that generated an abnormal fusion with nucleophosmin (NPM), i.e. NPM-MLF1 (1). The t(3;5) is found mainly in the M6 erythroleukemic subtype of acute myeloid leukemia (3). Significantly the fusion protein NPM-MLF1 is almost exclusively nuclear (1).The murine orthologue of MLF1 was isolated independently as hemopoietic lineage switch 7 (Hls7), a gene up-regulated when J2E erythroleukemic cells spontaneously developed a monoblastoid appearance (2, 4). Upon reintroduction into parental J2E cells, Hls7/Mlf1 induced a dramatic phenotypic change as the proerythroblastoid cells now displayed an immature, blast-like appearance (2). Hls7/Mlf1 has also been shown to influence hemopoietic lineage commitment by altering the balance between erythroid and myeloid progenitors (2). In contrast with the nuclear localization of the NPM-MLF1 fusion protein, Mlf1 is located primarily in the cytoplasm with some punctate nuclear staining (1, 2).Apart from a classical 14-3-3 binding site, Mlf1 has no recognizable motifs (1, 2, 5, 6). Therefore, yeast two-hybrid screens have been conducted to identify partner proteins that may elucidate the function of Mlf1. One molecule shown to bind Mlf1 was Mlf1 adaptor molecule (Madm), an adaptor protein involved in nuclear-cytoplasmic shuttling (7). Another Mlf1-binding protein is Mlf1-interacting protein/KSHV latent nuclear antigen-interacting protein (Mlf1IP/KLIP1), a novel nuclear molecule that may function as a transcriptional regulator (8, 9). Interestingly in Drosophila, Mlf1 associates with DNA replication-related element binding factor (DREF) (5), a DNAbinding protein that regulates genes involved in proliferation, including E2f (10). It has been suggested that "the DREF system may occupy an intersection in growth and differentiation signaling pathways" (11).Recently we have shown that Mlf1 interferes with erythropoieti...

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Section: Discussionmentioning

confidence: 99%

“…2C) and is most probably the murine orthologue of the chicken protein chicken hnRNP-U-like molecule (chURP) (30). The protein also contains a potential RNA-binding RGG motif (Fig.…”

Section: Mlf1mentioning

confidence: 99%

Myeloid Leukemia Factor 1 Associates with a Novel Heterogeneous Nuclear Ribonucleoprotein U-like Molecule

Winteringham

Endersby²,

Kobelke

et al. 2006

Journal of Biological Chemistry

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“…Predictably, the cytoplasmic 14‐3‐3 associated with HLS7 in this screen. In addition, HLS7 bound the murine homolog of the nuclear protein chURP, a molecule related to hnRNP U (Lodge et al ., 1999). Association with chURP, together with the appearance in discrete nuclear foci, indicates that HLS7 may have a functional role within the nucleus.…”

Section: Discussionmentioning

confidence: 99%

HLS7, a hemopoietic lineage switch gene homologous to the leukemia-inducing gene MLF1

et al. 1999

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Hemopoietic lineage switching occurs when leukemic cells, apparently committed to one lineage, change and display the phenotype of another pathway. cDNA representational difference analysis was used to identify myeloid-specific genes that may be associated with an erythroid to myeloid lineage switch involving the murine J2E erythroleukemic cell line. One of the genes isolated (HLS7) is homologous to the novel human oncogene myeloid leukemia factor 1 (MLF1) involved in the t(3;5)(q25.1;q34) translocation associated with acute myeloid leukemia. Enforced expression of HLS7 in J2E cells induced a monoblastoid phenotype, thereby recapitulating the spontaneous erythroid to myeloid lineage switch. HLS7 also inhibited erythropoietin-or chemically-induced differentiation of erythroleukemic cell lines and suppressed development of erythropoietin-responsive colonies in semi-solid culture. However, intracellular signaling activated by erythropoietin was not impeded by ectopic expression of HLS7. In contrast, HLS7 promoted maturation of M1 monoblastoid cells and increased myeloid colony formation in vitro. These data show that HLS7 can influence erythroid/myeloid lineage switching and the development of normal hemopoietic cells.

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Cyclin-dependent kinase 5 is a calmodulin-binding protein that associates with puromycin-sensitive aminopeptidase in the nucleus of Dictyostelium

Huber

Catalano

O’Day

2013

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Cyclin-dependent kinase 5 (Cdk5) is a serine/threonine kinase that has been implicated in a number of cellular processes. In Dictyostelium, Cdk5 localizes to the nucleus and cytoplasm, interacts with puromycin-sensitive aminopeptidase A (PsaA), and regulates endocytosis, secretion, growth, and multicellular development. Here we show that Cdk5 is a calmodulin (CaM)-binding protein (CaMBP) in Dictyostelium. Cdk5, PsaA, and CaM were all present in isolated nuclei and Cdk5 and PsaA co-immunoprecipitated with nuclear CaM. Although nuclear CaMBPs have previously been identified in Dictyostelium, the detection of CaM in purified nuclear fractions had not previously been shown. Putative CaM-binding domains (CaMBDs) were identified in Cdk5 and PsaA. Deletion of one of the two putative CaMBDs in Cdk5 ((132)LLINRKGELKLADFGLARAFGIP(154)) prevented CaM-binding indicating that this region encompasses a functional CaMBD. This deletion also increased the nuclear distribution of Cdk5 suggesting that CaM regulates the nucleocytoplasmic transport of Cdk5. A direct binding between CaM and PsaA could not be determined since deletion of the one putative CaMBD in PsaA prevented the nuclear localization of the deletion protein. Together, this study provides the first direct evidence for nuclear CaM in Dictyostelium and the first evidence in any system for Cdk5 being a CaMBP.

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Identification of chURP, a nuclear calmodulin‐binding protein related to hnRNP‐U

Cited by 5 publications

References 76 publications

Myeloid Leukemia Factor 1 Associates with a Novel Heterogeneous Nuclear Ribonucleoprotein U-like Molecule

Myeloid Leukemia Factor 1 Associates with a Novel Heterogeneous Nuclear Ribonucleoprotein U-like Molecule

HLS7, a hemopoietic lineage switch gene homologous to the leukemia-inducing gene MLF1

Cyclin-dependent kinase 5 is a calmodulin-binding protein that associates with puromycin-sensitive aminopeptidase in the nucleus of Dictyostelium

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