A Phosphoinositide Interacting Protein Coordinates Stress Precursor Activities.

Unlabelled: Samd14 is crucial for cell signaling and survival in mouse models of acute anemia. Samd14 has an N-terminal actin capping protein (CP) and a C-terminal sterile alpha motif (SAM) to coordinate stem cell factor/Kit and erythropoietin receptor signaling pathways during terminal differentiation of red blood cell precursors. Here we present new findings that Samd14 expression is needed to maintain balanced autophagy in red blood cell precursors following acute anemia.

The SAMD1 transcription factor coordinates hematopoietic lineage differentiation and H3K4 methylation status.

Cell progenitor to progeny transitions depend on precise transcriptional mechanisms to adjust gene expression. The sterile α-motif-containing 1 protein (SAMD1) regulates a shift in transcriptional activity during embryonic stem cell exit from pluripotency. SAMD1 interacts with, and facilitates the activity of, the histone H3 lysine-specific demethylase 1 (LSD1; a lysine demethylating enzyme).

Signaling mechanisms and cis -regulatory control of Samd14 in erythroid regeneration.

Purpose Of Review: This review evaluates the known mechanisms of regulating erythroid regeneration via the sterile alpha motif protein-14 ( Samd14 ) enhancer, Samd14's role in stem cell factor/Kit and erythropoietin (Epo) signaling, possible SAMD14 functions beyond erythropoiesis, and extrapolation to other anemia-response pathways.

Recent Findings: Samd14 expression is controlled by an anemia-activated E-box-GATA transcriptional enhancer required for erythroid regeneration, and the Samd14 protein is needed for acute anemia recovery. Samd14 interacts with actin capping proteins to elevate Kit signaling via MAPK and PI3K/Akt pathways in stress erythroid precursors and promotes Epo signaling at later stages.

Physiological and regenerative functions of sterile-α motif protein-14 in hematopoiesis.

Sterile α-motif domain-14 (Samd14) protein expression increases the regenerative capacity of the erythroid system. Samd14 is transcriptionally upregulated and promotes cell signaling via the receptor tyrosine kinase Kit in a critical window of acute erythroid regeneration. We generated a hematopoietic-specific conditional Samd14 knockout mouse model (Samd14-CKO) to study the role of Samd14 in hematopoiesis.

Ability of metformin to deplete NAD+ contributes to cancer cell susceptibility to metformin cytotoxicity and is dependent on NAMPT expression.

Background: Nicotinamide adenine dinucleotide (NAD+) is vital for not only energy metabolism but also signaling pathways. A major source of NAD+ depletion is the activation of poly (ADP-ribose) polymerase (PARP) in response to DNA damage. We have previously demonstrated that metformin can cause both caspase-dependent cell death and PARP-dependent cell death in the MCF7 breast cancer cells but not in the MDA-MB-231 (231) breast cancer cells while in high-glucose media.

Defining a cohort of anemia-activated cis elements reveals a mechanism promoting erythroid precursor function.

Acute anemia elicits broad transcriptional changes in erythroid progenitors and precursors. We previously discovered a cis-regulatory transcriptional enhancer at the sterile alpha motif domain-14 enhancer locus (S14E), defined by a CANNTG-spacer-AGATAA composite motif and occupied by GATA1 and TAL1 transcription factors, is required for survival in severe anemia. However, S14E is only 1 of dozens of anemia-activated genes containing similar motifs.

Functional requirements for a Samd14-capping protein complex in stress erythropoiesis.

Acute anemia induces rapid expansion of erythroid precursors and accelerated differentiation to replenish erythrocytes. Paracrine signals-involving cooperation between stem cell factor (SCF)/Kit signaling and other signaling inputs-are required for the increased erythroid precursor activity in anemia. Our prior work revealed that the sterile alpha motif (SAM) domain 14 () gene increases the regenerative capacity of the erythroid system in a mouse genetic model and promotes stress-dependent Kit signaling.