• Corpus ID: 38850498

MCL-1 S , a Splicing Variant of the Antiapoptotic BCL-2 Family Member MCL-1 , Encodes a Proapoptotic Protein Possessing Only the BH 3 Domain *

@inproceedings{Bae2000MCL1S,
  title={MCL-1 S , a Splicing Variant of the Antiapoptotic BCL-2 Family Member MCL-1 , Encodes a Proapoptotic Protein Possessing Only the BH 3 Domain *},
  author={Jeehyeon Bae and Chandra P. Leo and Sheau Yu Teddy Hsu and Aaron J W Hsueh},
  year={2000}
}
MCL-1 (myeloid cell leukemia-1) is an antiapoptotic BCL-2 family protein discovered as an early induction gene during myeloblastic leukemia cell differentiation. This survival protein has the BCL-2 homology (BH) domains 1, 2, and 3 and a C-terminal transmembrane region. We identified a short splicing variant of the MCL-1 mRNA in the human placenta encoding a protein, termed MCL-1 short (MCL-1S), with an altered C terminus as compared with the full-length MCL-1 long (MCL1L), leading to the loss… 

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A proteolytic fragment of Mcl-1 exhibits nuclear localization and regulates cell growth by interaction with Cdk1.

Overexpression of human Mcl-1 in a murine myeloid progenitor cell line resulted in a lower rate of proliferation and results suggest that binding to snM cl-1 alters the ability of Cdk1 to bind its conventional partner, cyclin B1.

Upregulation of Mcl-1S Causes Cell-Cycle Perturbations and DNA Damage Accumulation

Surprisingly, a small molecule inhibitor of Mcl-1, BH3-mimetic S63845, did not affect the cell cycle progression or the amount of DNA damage, suggesting that direct inhibition of M cl-1 is devoid of cell-cycle related undesired effects.

A novel Mcl1 variant inhibits apoptosis via increased Bim sequestration

This cloned variant of the anti-apoptotic Bcl2-family member Myeloid cell leukemia-1 (Mcl1) from human neuroblastoma and leukemia cells efficiently protects tumor cells against extrinsic death signalling and therefore may provide a survival advantage for highly aggressive tumors.

Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins.

The results indicate that Bak is held in check solely by Mcl-1 and Bcl-x(L) and induces apoptosis only if freed from both, and the finding that different prosurvival proteins have selective roles has notable implications for the design of anti-cancer drugs that target the B cl-2 family.

Re: Prognostic Signi fi cance of a Short Sequence Insertion in the MCL-1 Promoter in Chronic Lymphocytic Leukemia

DNA derived from 15 sets of paired lung cancer and adjacent normal lung tissue from patients undergoing routine thoracotomy for surgical resection of their malignancy was screened for the presence of the MCL-1 promoter insertions and found the +6 and +18 polymorphisms to be common, suggesting they contribute to oncogenesis by increasing the expression of M CL-1.

Interleukin-3 Stimulation of mcl-1 Gene Transcription Involves Activation of the PU.1 Transcription Factor through a p38 Mitogen-Activated Protein Kinase-Dependent Pathway

The results demonstrate that IL-3 stimulation of mcl-1 gene transcription through the SIE motif involves phosphorylation of PU.1 at serine 142 by a p38MAPK-dependent pathway.

Re: Prognostic Signifi cance of a Short Sequence Insertion in the MCL-1 Promoter in Chronic Lymphocytic Leukemia

DNA derived from 15 sets of paired lung cancer and adjacent normal lung tissue from patients undergoing routine thoracotomy for surgical resection of their malignancy was screened for the presence of the MCL-1 promoter insertions and found the +6 and +18 polymorphisms to be common, suggesting they contribute to oncogenesis by increasing the expression of M CL-1.

Mcl‐1 targeting could be an intriguing perspective to cure cancer

Mcl‐1 is a potent oncogene that is regulated at the transcriptional, posttranscriptional, and posttranslational levels and one of the key regulators of cancer stem cells’ self‐renewal that contributes to tumor survival.
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