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

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  • 1. Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
      Authors
    • Kozopas KM 1
    (1 author)

Proceedings of the National Academy of Sciences of the United States of America, 01 Apr 1993, 90(8):3516-3520
https://doi.org/10.1073/pnas.90.8.3516 PMID: 7682708 PMCID: PMC46331

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Abstract 

During their lifespan, immature cells normally pass through sequential transitions to a differentiated state and eventually undergo cell death. This progression is aberrant in cancer, although the transition to differentiation can be reestablished in inducible leukemia cell lines. This report describes a gene, MCL1, that we isolated from the ML-1 human myeloid leukemia cell line during phorbol ester-induced differentiation along the monocyte/macrophage pathway. Our results demonstrate that expression of MCL1 increases early in the induction, or "programming," of differentiation in ML-1 (at 1-3 hr), before the appearance of differentiation markers and mature morphology (at 1-3 days). They further show that MCL1 has sequence similarity to BCL2, a gene involved in normal lymphoid development and in lymphomas with the t(14;18) chromosome translocation. MCL1 and BCL2 do not fall into previously known gene families. BCL2 differs from many oncogenes in that it inhibits programmed cell death, promoting viability rather than proliferation; this parallels the association of MCL1 with the programming of differentiation and concomitant maintenance of viability but not proliferation. Thus, in contrast to proliferation-associated genes, expression of MCL1 and BCL2 relates to the programming of differentiation and cell viability/death. The discovery of MCL1 broadens our perspective on an emerging MCL1/BCL2 gene family and will allow further comparison with oncogene families.

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Proc Natl Acad Sci U S A. 1993 Apr 15; 90(8): 3516–3520.
PMCID: PMC46331
PMID: 7682708

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

K M Kozopas, T Yang, H L Buchan, P Zhou, and R W Craig
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Abstract

During their lifespan, immature cells normally pass through sequential transitions to a differentiated state and eventually undergo cell death. This progression is aberrant in cancer, although the transition to differentiation can be reestablished in inducible leukemia cell lines. This report describes a gene, MCL1, that we isolated from the ML-1 human myeloid leukemia cell line during phorbol ester-induced differentiation along the monocyte/macrophage pathway. Our results demonstrate that expression of MCL1 increases early in the induction, or "programming," of differentiation in ML-1 (at 1-3 hr), before the appearance of differentiation markers and mature morphology (at 1-3 days). They further show that MCL1 has sequence similarity to BCL2, a gene involved in normal lymphoid development and in lymphomas with the t(14;18) chromosome translocation. MCL1 and BCL2 do not fall into previously known gene families. BCL2 differs from many oncogenes in that it inhibits programmed cell death, promoting viability rather than proliferation; this parallels the association of MCL1 with the programming of differentiation and concomitant maintenance of viability but not proliferation. Thus, in contrast to proliferation-associated genes, expression of MCL1 and BCL2 relates to the programming of differentiation and cell viability/death. The discovery of MCL1 broadens our perspective on an emerging MCL1/BCL2 gene family and will allow further comparison with oncogene families.

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Selected References

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