A5101590640- Cancer, Hypoxia, and Metabolism
- Pancreatic function and diabetes
- RNA modifications and cancer
- PI3K/AKT/mTOR signaling in cancer
- Polyomavirus and related diseases
- Metabolism, Diabetes, and Cancer
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- Viral-associated cancers and disorders
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Tuberous Sclerosis Complex Research
Icahn School of Medicine at Mount Sinai
2024
UPMC Hillman Cancer Center
2019-2023
University of Pittsburgh
2019
Eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1) inhibits cap-dependent in eukaryotes by competing with eIF4G for an interaction eIF4E. Phosphorylation at Ser-83 of 4E-BP1 occurs during mitosis through the activity cyclin-dependent kinase (CDK1)/cyclin B rather than canonical mTOR activity. Here, we investigated eIF4E or interphase and mitosis. We observed that bind similar levels The most highly phosphorylated mitotic isoform (δ) did not interact eIF4E, whereas...
The RNA polymerase II (RNAPII) transcription cycle is regulated throughout its duration by reversible protein phosphorylation. elongation factor SPT5 contains two regions targeted cyclin-dependent kinase 9 (CDK9) and previously implicated in promoter-proximal pausing termination: the linker between KOWx-4 KOW5 domains carboxy-terminal repeat (CTR) 1, respectively. Here we show that phosphorylations KOWx-4/5 linker, CTR1 a third region, CTR2, coordinately control pause release, speed...
Objective Cyclin-dependent kinase 1 (CDK1)/cyclin B1 phosphorylates many of the same substrates as mTORC1 (a key regulator glucose metabolism), including eukaryotic initiation factor 4E-binding protein (4E-BP1). Only mitotic CDK1 4E-BP1 at residue S82 in mice (S83 humans), addition to common phospho-acceptor sites phosphorylated by both and mTORC1. We examined metabolism having a single aspartate phosphomimetic amino acid knock substitution serine 82 (4E-BP1 S82D ) mimicking constitutive...
4E-BP1 is a tumor suppressor regulating cap-dependent translation that in turn controlled by mechanistic target of rapamycin (mTOR) or cyclin-dependent kinase 1 (CDK1) phosphorylation. serine 82 (S82) phosphorylated CDK1, but not mTOR, and the consequences this mitosis-specific phosphorylation are unknown. Knock-in mice were generated with single S82 alanine (S82A) substitution leaving other sites intact. S82A fertile exhibited no gross developmental behavioral abnormalities, homozygotes...