MindMap Gallery Medicine [Key Literature] Collagen Pro-4-hydroxylase 1
This is an article about [Key Literature] Effects of Collagen Pro-4-hydroxylase 1 on HIF-1α Stability and TnBC Chemotherapy Resistance Collagen Pro-4-hydroxylase 1 on HIF-1α Stabilization and TnBC Chemotherapy Resistance Influence mind map
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This is a mind map about bacteria, and its main contents include: overview, morphology, types, structure, reproduction, distribution, application, and expansion. The summary is comprehensive and meticulous, suitable as review materials.
This is a mind map about plant asexual reproduction, and its main contents include: concept, spore reproduction, vegetative reproduction, tissue culture, and buds. The summary is comprehensive and meticulous, suitable as review materials.
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P4HA1-HIF1α
basic information
Research Background
Increased collagen production is associated with the development and progression of breast cancer, and stromal cells are the primary source of collagen deposition. The expression of collagen P4H is significantly upregulated during the occurrence and development of breast cancer, and the increased expression of P4HA is associated with poor prognosis. Interestingly, induction of P4HA1 expression in cancer cells is necessary for breast cancer metastasis
in conclusion
P4HA1 contributes most of the prolyl 4-hydroxylase activity Newly synthesized HIF-1α is rapidly hydroxylated at proline 402 and (Pro564) by the oxygen-dependent dioxygenase (PHD) family Proline hydroxylation induces HIF-1α ubiquitination and degradation, thereby shortening the half-life of HIF-1 protein
P4HA1 expression and HIF activation
Fig1.P4HA1 protein levels are significantly increased in TNBC
Verify the relationship between P4HA1 and tumors
P4HA1 expression
P4 and collagen
P4 and tumor cell growth
3D
Fig. 2 P4HA1 induces the HIF-1 pathway in breast cancer cells
Eliciting P4HA1 and HIF
P4 and gene enrichment
P4-Hypoxic response, glycolysis-HIF
P4-HIF
RT-PCR RNA levels
WB protein level
forward verification
reverse verification
knockout
inhibitor
P4-HIF activity
cis-acting element
P4-HRE
knockout
inhibitor
HIF target genes
LDHA, PDK1
Hydroxylation and HIF-1α stability
Fig. 3 P4HA1 enhances HIF-1α protein stability
Demonstrate the relationship between P4HA1 and HIF degradation factors
P4HA1 In the presence of active PHD, HIF-1α protein is hydroxylated Becomes a target for degradation by the ubiquitin-proteasome system
degradation
ubiquitination
proteasome
P4HA1 increases HIF-1α protein levels by reducing ubiquitination-mediated protein degradation
HIF hydroxylation
PHD
P4HA1 increases HIF-1α protein levels by reducing PHD2-dependent proline hydroxylation
Fig. 4 P4HA1 enhances HIF-1α stability by modulating α-KG l and succinate levels
Elucidate the mechanism of P4HA1 and HIF
P4HA1 expression may be altered by Co-substrate α-KG and/or product succinate or the concentration of related metabolites affects the activity of PHD
P4-KG, succinic acid
KG-HIF
P4HA1 activates the HIF-1 pathway by reducing HIF-1α degradation, and this regulation is mediated through the metabolites α-KG and succinate
Tumor environment verification mechanism
P4HA1 and tumors
tumor initiating cells
tumor sphere
High Oxygen Consumption Rate (OCR)
transfer
drug sensitivity
Health letter