Related Experiment Video

Updated: Jun 4, 2026

Purification of Human S100A12 and Its Ion-induced Oligomers for Immune Cell Stimulation
12:55

Purification of Human S100A12 and Its Ion-induced Oligomers for Immune Cell Stimulation

Published on: September 29, 2019

Regulation of S100A10 by the PML-RAR-α oncoprotein

Paul A O'Connell1, Patricia A Madureira, Jason N Berman

  • 1Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, NS, USA.

Blood
|February 12, 2011
PubMed

Insights

S100A10, a plasminogen receptor on acute promyelocytic leukemia (APL) cells, drives excessive fibrinolysis and bleeding. All-trans retinoic acid (ATRA) treatment down-regulates S100A10, reducing fibrinolysis and improving APL outcomes.

Area of Science:

  • Hematology
  • Molecular Biology
  • Oncology

Background:

  • Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia characterized by the PML-RAR-α oncoprotein.
  • APL patients often experience severe bleeding due to excessive fibrinolysis.
  • All-trans retinoic acid (ATRA) is an effective treatment for APL, inducing PML-RAR-α oncoprotein destruction.

Purpose of the Study:

  • To investigate the role of S100A10 in APL-associated fibrinolysis.
  • To determine the effect of ATRA on S100A10 expression in APL cells.
  • To establish a link between S100A10, fibrinolysis, and the hemorrhagic complications in APL.

Main Methods:

  • Assessed S100A10 expression on the surface of APL cells.
  • Measured fibrinolytic activity in response to ATRA treatment and PML-RAR-α oncoprotein induction.
  • Utilized RNA interference to deplete S100A10 and evaluate its impact on fibrinolytic activity.

Main Results:

  • S100A10 was identified as a cell surface plasminogen receptor on APL cells.
  • ATRA treatment rapidly down-regulated S100A10, correlating with reduced fibrinolytic activity.
  • PML-RAR-α oncoprotein induction increased S100A10 expression and fibrinolytic activity, which was blocked by S100A10 depletion.

Conclusions:

  • S100A10 plays a critical role in cell surface plasmin generation and fibrinolysis in APL.
  • S100A10 is a key mediator linking the PML-RAR-α oncoprotein to the excessive fibrinolysis observed in APL.
  • Targeting S100A10 may offer a therapeutic strategy to mitigate hemorrhagic complications in APL.

More Related Videos

Expression, Purification, and Antimicrobial Activity of S100A1211:10

Expression, Purification, and Antimicrobial Activity of S100A12

Published on: May 13, 2017

Primary Sjogren's Syndrome Associated with Lung Adenocarcinoma: Probing the Potential Common Pathogenic Mechanisms and Experimental Verification10:21

Primary Sjogren's Syndrome Associated with Lung Adenocarcinoma: Probing the Potential Common Pathogenic Mechanisms and Experimental Verification

Published on: September 20, 2024

Related Concept Videos

Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...