Regulation of Mcl-1 alternative splicing by hnRNP F, H1 and K in breast cancer cells.

ABSTRACT: Myeloid cell leukemia-1 (Mcl -1) is one of the most frequently amplified genes in cancer, and its overexpression is associated with poor prognosis and drug resistance. As a member of the Bcl-2 family it is involved in the control of the mitochondrial (intrinsic) cell death pathway. Alternative splicing of the (Mcl-1) gene results in the expression of two functionally distinct proteins, the anti-apoptotic Mcl-1_L (exon 2 included) and the pro-apoptotic Mcl-1_S (exon 2 skipped). Our data shows that transfecting siRNAs that target hnRNP K and the hnRNP F/H family result in a switch in splicing towards the pro-apoptotic Mcl-1_S. Specific binding sites for these and other Mcl-1 splicing factors were investigated and identified by RNA immunoprecipitation and through

SUBMITTER: Tyson-Capper A 

PROVIDER: S-EPMC6333436 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature