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MCL1, a gene expressed in programmed myeloid cell differentiation, has sequence similarity to BCL2.
Open accessAbstract
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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Metadata
- Authors
- Kozopas, K. M., Yang, T., Buchan, H. L., Zhou, P., & Craig, R. W.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1993-04-15
- Volume
- 90
- Issue
- 8
- Pages
- 3516-3520
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1973363947
- Cited by
- 961
- References
- 2
- FWCI
- 14.36
- Type
- journal article
- Language
- en
- Open access
- bronze
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