MCL1, a gene expressed in programmed myeloid cell differentiation, has sequence similarity to BCL2.

Kozopas, Karen M.; Yang, Tao; Buchan, Heather L.; Zhou, Ping; Craig, Ruth W.

doi:10.1073/pnas.90.8.3516

Cited by 876 publications

(707 citation statements)

References 40 publications

Supporting

Mentioning

678

Contrasting

Unclassified

Order By: Relevance

“…We found that overexpression of Mcl-1 protected CE81T/VGH cells from staurosporine-induced apoptosis and transfection of a Mcl-1 antisense plasmid substantially increased the percentage of apoptotic cells (Figure 7). Our data support the fact that Mcl-1 is an inducible, antiapoptotic protein, as previously described in myeloid cells induced by TPA and GM-CSF (Kozopas et al, 1993;Chao et al, 1998), and in EBV immortalized B cells induced by IL-6 (Altmeyer et al, 1997). While the induction of Mcl-1 by TPA was mediated through the MAP kinase pathway in myeloblastic leukemia cells (Townsend et al, 1998), the IL-3 activation of mcl-1 gene expression was mediated via PI3-K-Akt-dependent andindependent pathways in murine pro-B Ba/F3 cells (Wang et al, 1999).…”

Section: Discussionsupporting

confidence: 92%

Epidermal growth factor (EGF) suppresses staurosporine-induced apoptosis by inducing mcl-1 via the mitogen-activated protein kinase pathway

Leu¹,

Chang²,

Hu³

2000

Oncogene

View full text Add to dashboard Cite

Overexpression of epidermal growth factor receptor (EGFR) and establishment of transforming growth factor a (TGF a)/EGF autocrine system are frequently detected in tumor cells. In addition to mitogenic ability, we demonstrate in this report that EGF protects a human esophageal carcinoma (CE) cell line, CE81T/VGH, from staurosporine-induced apoptosis. The anti-apoptotic signal of EGF is alleviated by a MEK inhibitor PK98059 or an ERK2 dominant negative mutant but not by a phosphatidylinositol-3'-kinase (PI-3K) inhibitor wortmannin. Furthermore, v-raf blocks apoptosis induced by staurosporine. This evidence implies that the survival signal of EGF is mediated via the Raf-MEK-ERK pathway but not the PI3-K pathway. The survival e ect of EGF is coincident with the induction of mcl-1, an antiapoptotic gene in the bcl-2 family. PD98059 also suppresses the induction of Mcl-1 by EGF, implying that EGF may up-regulate Mcl-1 via the MAP kinase pathway. Overexpression of mcl-1 is su cient to protect against apoptosis, while transfection of a mcl-1 antisense plasmid causes cell death. The expression of mcl-1 antisense plasmid also suppresses the anti-apoptotic e ect of EGF. Taken together, these results indicate that EGF may up-regulate Mcl-1 through the MAP kinase pathway to suppress apoptosis.

show abstract

Section: Discussionsupporting

confidence: 92%

Epidermal growth factor (EGF) suppresses staurosporine-induced apoptosis by inducing mcl-1 via the mitogen-activated protein kinase pathway

Leu¹,

Chang²,

Hu³

2000

Oncogene

View full text Add to dashboard Cite

show abstract

“…As shown in Figure 1, we observed a dramatic increase in both MCL1 transcripts in ML-1 cells (3.8 and 2.4 kb; Kozopas et al, 1993). We also observed an increase in the WMN Burkitt's lymphoma cell line, which is similar to ML-1 in that p53 is wildtype and the cells respond to IR with increases in GADD45 and BAX (Zhan et al, 1996).…”

Section: Resultssupporting

confidence: 63%

“…Under both di erentiation-inducing and cytotoxic conditions, the expression of MCL1 increased rapidly, elevation of the MCL1 mRNA being seen within 1 ± 3 h and that of the protein at 3 ± 6 h (Kozopas et al, 1993;. The increase in MCL1 preceded di erentiation or death, which were detectable morphologically within 1 day and continued over approximately 3 days.…”

Section: Introductionmentioning

confidence: 96%

“…Another member of the BCL2 family, MCL1, was discovered based upon increased expression in ML-1 cells undergoing di erentiation in response to the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) (Kozopas et al, 1993). Like Bcl2 (Hockenbery et al, 1990;Vaux et al, 1988), transfection with Mcl1 can delay cell death under conditions that cause apoptosis (Reynolds et al, 1994(Reynolds et al, , 1996Zhou et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Induction of BCL2 family member MCL1 as an early response to DNA damage

et al. 1997

View full text Add to dashboard Cite

When ML-1 human myeloid leukemia cells are exposed to DNA damaging agents, they exhibit dramatic changes in the expression of a variety of gene products. This includes an increase in p53 (wild-type), a decrease in BCL2, a p53-dependent increase in the BCL2 family member BAX, and increases in Growth Arrest and DNA Damage-inducible (GADD) genes such as GADD45; these changes occur as early events in a sequence that culminates in DNA damage-induced apoptosis. DNA damaging agents have now been tested for e ects on expression of another BCL2 family member, MCL1, a gene expressed during ML-1 cell di erentiation. Expression of MCL1 was found to increase upon exposure of ML-1 cells to various types of DNA damaging agents, including ionizing radiation, ultraviolet radiation, and alkylating drugs. The increase in MCL1 occurred rapidly and was transient, levels of the MCL1 mRNA being elevated within 4 h and having returned to near baseline within 24 h. An increase in the Mcl1 protein was also seen, with the maximal increase occurring at an intermediate dose of IR (5 Gray) and lesser increases occurring at either lower or higher doses. The increase in expression of MCL1 was further studied using a panel of human cell lines that includes cells containing or not containing alterations in p53 as well as cells sensitive or insensitive to the apoptosis-inducing e ects of DNA damage. The DNA damage-induced increase in MCL1 mRNA did not depend upon p53 as it was seen in cells lacking functional p53. However, the increase did depend upon susceptibility to apoptosis as it was not seen in cells insensitive to apoptosis-induction by DNA damaging agents. These ®ndings demonstrate that cytotoxic DNA damage causes an increase in the expression of MCL1 along with increases in GADD45 and BAX and a decrease in BCL2. Furthermore, while the increase in GADD45 is seen both in cells that undergo growth arrest and in cells that undergo apoptosis in response to DNA damage, alterations in the pro®le of expression of BCL2 family members occur exclusively in cells that undergo the apoptotic response, with some family members increasing through p53-dependent (BAX) and others through p53-independent (MCL1) pathways. Overall, expression MCL1 can increase during the induction of cell death as well as during the induction of di erentiation.

show abstract

“…This implies the existence of other gene family members also involved in the regulation of apoptosis. A number of other cellular proteins including Bax (Oltvai et al, 1993), Bcl-x (Boise et al, 1993), Bak (Chittenden et al, 1995;Kiefer et al, 1995), Mcl-1 (Kozopas et al, 1993) and A1 (Lin et al, 1993) share highly conserved domains (BH-1 and BH-2; Oltvai et al, 1993) with Bcl-2. Bax is capable of forming homodimers and heterodimers with Bcl-2.…”

Section: Melanoma; Fish Analysismentioning

confidence: 99%

GRS, a novel member of the Bcl-2 gene family, is highly expressed in multiple cancer cell lines and in normal leukocytes

et al. 1997

View full text Add to dashboard Cite

MCL1, a gene expressed in programmed myeloid cell differentiation, has sequence similarity to BCL2.

Cited by 876 publications

References 40 publications

Epidermal growth factor (EGF) suppresses staurosporine-induced apoptosis by inducing mcl-1 via the mitogen-activated protein kinase pathway

Epidermal growth factor (EGF) suppresses staurosporine-induced apoptosis by inducing mcl-1 via the mitogen-activated protein kinase pathway

Induction of BCL2 family member MCL1 as an early response to DNA damage

GRS, a novel member of the Bcl-2 gene family, is highly expressed in multiple cancer cell lines and in normal leukocytes

Contact Info

Product

Resources

About