A 22-kd protein (sorcin/V19) encoded by an amplified gene in multidrug-resistant cells, is homologous to the calcium-binding light chain of calpain.

Bliek, Alexander M. van der; Meyers, Marian B.; Biedler, June L.; Hes, E.; Borst, Piet

doi:10.1002/j.1460-2075.1986.tb04630.x

Cited by 141 publications

(96 citation statements)

References 66 publications

(40 reference statements)

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“…These findings are consistent with the presence of two EF-hand calcium binding motifs and two putative protein kinase A recognition sites in the C-terminal domain of the sorcin sequence [4]. The N-terminal domain of the sequence is rich in glycine, proline and tyrosine residues and is homologous to the corresponding domain of the calpain light chain where it is involved in heterodimer formation [4].…”

Section: Introductionsupporting

confidence: 67%

“…Direct calcium binding studies and in vitro phosphorylation assays have shown that sorcin purified from heart and sorcin-overproducing cultured cells binds Ca 2+ and is phosphorylated by the protein kinase A catalytic subunit [1,5,7,8]. These findings are consistent with the presence of two EF-hand calcium binding motifs and two putative protein kinase A recognition sites in the C-terminal domain of the sorcin sequence [4]. The N-terminal domain of the sequence is rich in glycine, proline and tyrosine residues and is homologous to the corresponding domain of the calpain light chain where it is involved in heterodimer formation [4].…”

Section: Introductionmentioning

confidence: 65%

“…in E. coli Full-length sorcin cDNA, isolated from a colchicine-resistant Chinese hamster ovary library, was a gift from Dr. Piet Borst from The Netherlands Cancer Institute [4]. It was amplified by the polymerase chain reaction (PCR) utilizing primers that contained restriction sites NcoI and HindIlI and were synthesized by the solid-phase triester method.…”

Section: Preparation Of the Pkt7sor Cin Vector And Expression Of R-somentioning

confidence: 99%

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Calcium‐dependent translocation of sorcin to membranes: functional relevance in contractile tissue

Meyers

Zamparelli²,

Verzili³

et al. 1995

FEBS Letters

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Sorcin, a 22 kDa calcium binding protein present in abundance in cardiac tissue and in multi-drug resistant cells and previously described as a soluble protein, is now shown to undergo a calcium-dependent translocation process from the cytosol to cellular membranes in both systems. The translocation process takes place also in E. coli BL21 cells that express recombinant sorcin, r-sorcin, and can be exploited in the purification of the protein. Calcium binding to purified r-sorcin occurs at micromolar concentrations of the metal and is accompanied by a conformational change that renders the protein soluble in the non-ionic detergent Triton X-114. This finding suggests that lipids are the target of sorcin on cellular membranes. The possible significance of the calcium-dependent translocation of sorcin in the specialized functions of sorcin-expressing cells is discussed.

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Section: Introductionsupporting

confidence: 67%

Section: Introductionmentioning

confidence: 65%

Section: Preparation Of the Pkt7sor Cin Vector And Expression Of R-somentioning

confidence: 99%

See 1 more Smart Citation

Calcium‐dependent translocation of sorcin to membranes: functional relevance in contractile tissue

Meyers

Zamparelli²,

Verzili³

et al. 1995

FEBS Letters

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“…From sequence comparisons it appeared that the ALG-2 protein contains five EF-hands, with two of them being functional in 45 Ca 2ϩ overlay experiments (13), and furthermore it shares homology with members of the PEF (penta EF-hand) family, which includes sorcin (16), grancalcin (17), calpain light chain (18), yeast hypothetical protein of 38.4 kDa (19), and peflin (20). These proteins contain a glycine-rich N-terminal region proposed to play an important role in Ca 2ϩ -dependent membrane binding (19).…”

mentioning

confidence: 99%

Two Forms of the Apoptosis-linked Protein ALG-2 with Different Ca2+ Affinities and Target Recognition

Tarabykina¹,

Møller²,

Durussel³

et al. 2000

Journal of Biological Chemistry

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“…Studies using in vitro derived multidrugresistant (MDR) cell lines have shown that MDR is often associated with over-production of two groups of proteins: the P-glycoproteins (for review see which have drug-binding properties (Safa et al, 1986) and are thought to function as a membrane anchored efflux pump for multiple drugs (Willingham et al, 1986); and sorcin/CP22 (Meyers et al, 1985;Meyers & Biedler, 1981;Koch et al, 1986;Martinnson et al, 1985;Shen et al, 1986a; Van der Bliek et al, 1986a), a small cytosolic calcium-binding protein. Considerable evidence supports the hypothesis that it is P-glycoprotein that is responsible for MDR in almost all cell lines examined (Debenham et al, 1982;Gros et al, 1986;Kartner et al, 1983;Robertson et al, 1984;Scotto et al, 1986;Shen et al, 1986b;Van der Bliek et al, 1986b).…”

mentioning

confidence: 99%

Amplification and expression of mdr1 gene in a multidrug resistant variant of small cell lung cancer cell line NCI-H69

Reeve

Rabbitts²,

Twentyman³

1989

Br J Cancer

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Summary Amplification and expression of the mdrl gene encoding P-glycoprotein have been studied in H69/LX4 a multidrug resistant variant (MDR) of small cell lung cancer (SCLC) cell line NCI-H69. Recently a second independently derived MDR variant of this cell line designated H69/AR was found by others not to show amplification, rearrangement or over-expression of the mdrl gene. The present study reports that in marked contrast to H69/AR, H69/LX4 shows amplification and expression of the P-glycoprotein gene and raises the possibility that P-glycoprotein hyperexpression may be a clinically relevant component of MDR in some SCLC tumours.Resistance of tumours to multiple drugs is a major problem in cancer treatment. Studies using in vitro derived multidrugresistant (MDR) cell lines have shown that MDR is often associated with over-production of two groups of proteins: the P-glycoproteins (for review see which have drug-binding properties (Safa et al., 1986) al., 1982;Gros et al., 1986;Kartner et al., 1983;Robertson et al., 1984;Scotto et al., 1986;Shen et al., 1986b;Van der Bliek et al., 1986b).In an effort to elucidate mechanisms of MDR in human small cell lung cancer (SCLC), multidrug resistant variants (MDR) of human SCLC cell line NCI-H69, have recently been derived following cell culture in increasing doses of adriamycin (ADM) Mirksi et al., 1987). Surprisingly, the MDR variant H69/AR (Mirski et al., 1987) does not show amplification, rearrangement or overexpression of the P-glycoprotein gene (Trent et al., 1988) suggesting that other factors are responsible for the MDR phenotype in these cells. The present study investigates Pglycoprotein gene amplification and expression in H69/LX4 (Twentyman et al., 1986) a second, independently derived MDR variant of NCI-H69. We report that, in marked contrast to H69/AR cells, amplification and hyperexpression of P-glycoprotein gene occurs in this MDR cell line. Materials and methods Cell linesThe SCLC cell line NCI-H69 (kindly supplied by Drs Desmond Carney and Adi Gazdar of the NCI Navy Medical Oncology Branch, Bethesda, MD) was derived from a patient who had previously received multidrug therapy (including ADM).Full details of the in vitro derivation of the MDR variant of NCI-H69 are given elsewhere . Briefly, NCI-H69 parent (H69P) cells were initially exposed to 0.02 pgml-1 ADM and then transferred to 0.04pgml-1 ADM after 3 weeks. After a further 4 weeks, ADM was removed and when cell growth resumed, ADM was reintroduced at weekly increasing doses of 0.1, 0.2 and

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A 22-kd protein (sorcin/V19) encoded by an amplified gene in multidrug-resistant cells, is homologous to the calcium-binding light chain of calpain.

Cited by 141 publications

References 66 publications

Calcium‐dependent translocation of sorcin to membranes: functional relevance in contractile tissue

Calcium‐dependent translocation of sorcin to membranes: functional relevance in contractile tissue

Two Forms of the Apoptosis-linked Protein ALG-2 with Different Ca2+ Affinities and Target Recognition

Amplification and expression of mdr1 gene in a multidrug resistant variant of small cell lung cancer cell line NCI-H69

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