Activation of RASSF2A by p300 induces late apoptosis through histone hyperacetylation

Chungang Liu1, Yunhui Pan, Xiuli Wang

  • 1School of Life Science, Northeast Normal University, Changchun 130024, Peoples Republic of China.

Insights

p300 protein induces late apoptosis by increasing Ras-associated family 2A (RASSF2A) expression in gastric cancer cells. This occurs via Sp1 transcription factor cooperation and histone acetylation at the RASSF2A promoter.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Ras-associated family 2A (RASSF2A) and p300 are involved in apoptosis.
  • The precise relationship between RASSF2A and p300 in apoptosis induction is not well understood.

Purpose of the Study:

  • To investigate the interrelationship between p300 and RASSF2A in the induction of apoptosis.
  • To elucidate the molecular mechanisms by which p300 influences RASSF2A expression and subsequent apoptosis.

Main Methods:

  • Cell culture of human gastric cancer SGC-7901 (p53-mutant) and 293T cells.
  • Analysis of RASSF2A expression and apoptosis induction.
  • Chromatin immunoprecipitation (ChIP) assays to assess histone acetylation and protein binding.
  • Investigation of the role of transcription factor Sp1.

Main Results:

  • p300 induces late apoptosis through up-regulation of RASSF2A in SGC-7901 cells.
  • p300 stimulates RASSF2A expression in 293T cells, cooperating with Sp1.
  • p300 induces histone H3 and H4 hyperacetylation at the RASSF2A promoter.
  • p300 and Sp1 exhibit reciprocal facilitation of binding to the RASSF2A promoter.

Conclusions:

  • Sp1-mediated RASSF2A gene transcription is activated by p300 via histone acetylation.
  • This p300-mediated activation of RASSF2A plays a significant role in inducing late apoptosis.

Related Concept Videos

The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...