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Titolo:
Microtubule-targeting drugs induce Bcl-2 phosphorylation and association with Pin1
Autore:
Pathan, N; Aime-sempe, C; Kitada, S; Haldar, S; Reed, JC;
Indirizzi:
Burnham Inst, La Jolla, CA 92037 USA Burnham Inst La Jolla CA USA 92037Burnham Inst, La Jolla, CA 92037 USA Univ Cincinnati, Cleveland, OH 44109 USA Univ Cincinnati Cleveland OH USA44109 incinnati, Cleveland, OH 44109 USA
Titolo Testata:
NEOPLASIA
fascicolo: 1, volume: 3, anno: 2001,
pagine: 70 - 79
SICI:
1522-8002(200101/02)3:1<70:MDIBPA>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
TAXOL-INDUCED APOPTOSIS; PROTEIN-KINASE PATHWAY; LEUKEMIA-CELL LINE; RAF-1/BCL-2 PHOSPHORYLATION; FAMILY PROTEINS; GROWTH ARREST; CANCER-CELLS; ONCOPROTEIN; DOMAIN; SUPPRESSION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
57
Recensione:
Indirizzi per estratti:
Indirizzo: Reed, JC Burnham Inst, 10901 N Torrey Pines, La Jolla, CA 92037 USA Burnham Inst 10901 N Torrey Pines La Jolla CA USA 92037 92037 USA
Citazione:
N. Pathan et al., "Microtubule-targeting drugs induce Bcl-2 phosphorylation and association with Pin1", NEOPLASIA, 3(1), 2001, pp. 70-79

Abstract

Bcl-2 is a critical suppressor of apoptosis that is overproduced in many types of cancer. Phosphorylation of the Bcl-2 protein is induced on serine residues in tumor cells arrested by microtubule-targeting drugs (paclitaxel,vincristine, nocodazole) and has been associated with inactivation of antiapoptotic function through an unknown mechanism. Comparison of a variety ofpharmacological inhibitors of serine/threonine-specific protein kinases demonstrated that the cyclin-dependent kinase inhibitor, flavopiridol, selectively blocks Bcl-2 phosphorylation induced by antimicrotubule drugs. Bcl-2 could also be coimmunoprecipitated with the kinase Cdc2 in M-phase-arrestedcells, suggesting that a Cdc2 may be responsible for phosphorylation of Bcl-2 in cells treated with microtubule-targeting drugs. Examination of several serine-->alanine substitution mutants of Bcl-2 suggested that serine 70 and serine 87 represent major sites of Bcl-2 phosphorylation induced in response to microtubule-targeting drugs. Both these serines are within sequence contexts suitable for proline-directed kinases such as Cdc2, Phosphorylated Bcl-2 protein was discovered to associate in Rn-phase-arrested cells with Pin1,a mitotic peptidyl prolyl isomerase (PPlase) known to interact with substrates of Cdc2 during mitosis, In contrast, phosphorylation of Bcl-2 induced by microtubule-targeting drugs did not alter its ability to associatewith Bcl-2 (homodimerization), Bax, BAG1, or other Bcl-2-binding proteins. Since the region in Bcl-2 containing serine 70 and serine 87 represents a proline-rich loop that has been associated with autorepression of its antiapoptotic activity, the discovery of Pin1 interactions with phosphorylated Bcl-2 raises the possibility that Pin1 alters the conformation of Bcl-2 and thereby modulates its function in cells arrested with antimicrotubule drugs.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 02:28:02