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The apoptosis-associated gamma-ray response of BCL-X(L) depends on normal p53 function.
Oncogene 1996; 13(10):2287-93O

Abstract

We have investigated the effect of DNA damage on the expression of BCL-X, a member of the BCL-2 family. BCL-X mRNA levels were found to increase upon exposure human cells to ionizing radiation (IR). The Bcl-X(L) protein, but not Bcl-X(S), was identified to be induced by IR. Like BAX, another member of the BCL-2 family and a p53-regulated gene, the induction of BCL-X(L) was dependent on normal p53 function and required that cells have an apoptosis-susceptible phenotype. The induction of BCL-X(L) was rapid, transient and dose-dependent. The mRNA level peaked at 4 h and returned to baseline by 24 h post-irradiation. In agreement with the increased transcript level, Bcl-X(L) protein level was also observed to increase in cells with wild-type p53 where IR triggered apoptosis. In addition, a survey of the BCL-X(L) mRNA basal levels in human cells with known apoptotic responses showed that low basal levels of BCL-X(L) mRNA in cells were highly correlated with a strong ability of cells to undergo IR-induced apoptosis. On the other hand, high levels of basal BCL-X(L) were correlated with the resistance of cells to IR-induced apoptosis regardless of p53 status. These results indicate that BCL-2 and BCL-X(L) behave differently in response to DNA damage treatment even though they both are able to protect cells from p53-mediated apoptosis; along with down-regulation of BCL-2, BCL-X(L) was up-regulated by IR in human cells with wild-type p53 and susceptibility to IR-induced apoptosis. We speculate that the physiological function of increased BCL-X(L) protein would be expected to probably limit the severity and length of BAX effect in order to maintain a proper threshold for apoptosis and to complete cell cycle arrest activated by p53.

Authors+Show Affiliations

Division of Basic Sciences, National Cancer Institute, Bethesda, MD 20892-4255, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

8950997

Citation

Zhan, Q, et al. "The Apoptosis-associated Gamma-ray Response of BCL-X(L) Depends On Normal P53 Function." Oncogene, vol. 13, no. 10, 1996, pp. 2287-93.
Zhan Q, Alamo I, Yu K, et al. The apoptosis-associated gamma-ray response of BCL-X(L) depends on normal p53 function. Oncogene. 1996;13(10):2287-93.
Zhan, Q., Alamo, I., Yu, K., Boise, L. H., Cherney, B., Tosato, G., ... Fornace, A. J. (1996). The apoptosis-associated gamma-ray response of BCL-X(L) depends on normal p53 function. Oncogene, 13(10), pp. 2287-93.
Zhan Q, et al. The Apoptosis-associated Gamma-ray Response of BCL-X(L) Depends On Normal P53 Function. Oncogene. 1996 Nov 21;13(10):2287-93. PubMed PMID: 8950997.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The apoptosis-associated gamma-ray response of BCL-X(L) depends on normal p53 function. AU - Zhan,Q, AU - Alamo,I, AU - Yu,K, AU - Boise,L H, AU - Cherney,B, AU - Tosato,G, AU - O'Connor,P M, AU - Fornace,A J,Jr PY - 1996/11/21/pubmed PY - 2001/3/28/medline PY - 1996/11/21/entrez SP - 2287 EP - 93 JF - Oncogene JO - Oncogene VL - 13 IS - 10 N2 - We have investigated the effect of DNA damage on the expression of BCL-X, a member of the BCL-2 family. BCL-X mRNA levels were found to increase upon exposure human cells to ionizing radiation (IR). The Bcl-X(L) protein, but not Bcl-X(S), was identified to be induced by IR. Like BAX, another member of the BCL-2 family and a p53-regulated gene, the induction of BCL-X(L) was dependent on normal p53 function and required that cells have an apoptosis-susceptible phenotype. The induction of BCL-X(L) was rapid, transient and dose-dependent. The mRNA level peaked at 4 h and returned to baseline by 24 h post-irradiation. In agreement with the increased transcript level, Bcl-X(L) protein level was also observed to increase in cells with wild-type p53 where IR triggered apoptosis. In addition, a survey of the BCL-X(L) mRNA basal levels in human cells with known apoptotic responses showed that low basal levels of BCL-X(L) mRNA in cells were highly correlated with a strong ability of cells to undergo IR-induced apoptosis. On the other hand, high levels of basal BCL-X(L) were correlated with the resistance of cells to IR-induced apoptosis regardless of p53 status. These results indicate that BCL-2 and BCL-X(L) behave differently in response to DNA damage treatment even though they both are able to protect cells from p53-mediated apoptosis; along with down-regulation of BCL-2, BCL-X(L) was up-regulated by IR in human cells with wild-type p53 and susceptibility to IR-induced apoptosis. We speculate that the physiological function of increased BCL-X(L) protein would be expected to probably limit the severity and length of BAX effect in order to maintain a proper threshold for apoptosis and to complete cell cycle arrest activated by p53. SN - 0950-9232 UR - https://www.unboundmedicine.com/medline/citation/8950997/The_apoptosis_associated_gamma_ray_response_of_BCL_X_L__depends_on_normal_p53_function_ DB - PRIME DP - Unbound Medicine ER -