biology

PELP-1

PELP-1 is a biology topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand PELP-1 rather than just read about it. In short: Proline-, glutamic acid- and leucine-rich protein 1 (PELP1) also known as modulator of non-genomic activity of estrogen receptor (MNAR) and transcription factor HMX3 is a protein that in humans is encoded by the PELP1 gene. is a transcriptional corepressor for nuclear receptors such as glucocorticoid receptors and a coactivator for estrogen receptors. Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) is t…

Key takeaways

PELP-1 belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect PELP-1 to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of PELP-1 from memory before moving on to harder problems.

Reference excerpt

Proline-, glutamic acid- and leucine-rich protein 1 (PELP1) also known as modulator of non-genomic activity of estrogen receptor (MNAR) and transcription factor HMX3 is a protein that in humans is encoded by the PELP1 gene. is a transcriptional corepressor for nuclear receptors such as glucocorticoid receptors and a coactivator for estrogen receptors. Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) is transcription coregulator and modulates functions of several hormonal receptors and transcription factors. PELP1 plays essential roles in hormonal signaling, cell cycle progression, and ribosomal biogenesis. PELP1 expression is upregulated in several cancers; its deregulation contributes to hormonal therapy resistance and metastasis; therefore, PELP1 represents a novel therapeutic target for many cancers.

Gene PELP1 is located on chromosome 17p13.2 and PELP1 is expressed in a wide variety of tissues; its highest expression levels are found in the brain, testes, ovaries, and uterus. Currently, there are two known isoforms (long 3.8 Kb and short 3.4 Kb) and short isoform is widely expressed in cancer cells.

Structure The PELP1 protein encodes a protein of 1130 amino acids, and exhibits both cytoplasmic and nuclear localization depending on the tissue. PELP1 lacks known enzymatic activity and functions as a scaffolding protein. It contains 10 NR-interacting boxes (LXXLL motifs) and functions as a coregulator of several nuclear receptors via its LXXLL motifs including ESR1, ESR2, ERR-alpha, PR, GR, AR, and RXR. PELP1 also functions as a coregulator of several other transcription factors, including AP1, SP1, NFkB, STAT3, and FHL2. PELP1 has a histone binding domain and interacts with chromatin-modifying complexes, including CBP/p300, histone deacetylase 2, histones, SUMO2, lysine-specific demethylase 1 (KDM1), PRMT6, and CARM1. PELP1 also interacts with cell cycle regulators such as pRb. E2F1, and p53. PELP1 is phosphorylated by hormonal and growth factor signals. PELP1 phosphorylation status is also influenced by cell cycle progression, and it is a substrate of CDKs. Further, PELP1 is phosphorylated by DNA damage induced kinases (ATM, ATR, DNA-PKcs).

Function PELP1 functions as a coactivator of several NRs and regulates genes involved in proliferation and cancer progression. PELP1 enhances transcription functions of ESR1, ESR2, AR, GR, E2F and STAT3. PELP1 participates in activation of ESR1 extra-nuclear actions by coupling ESR1 with Src kinase PI3K STAT3 ILK1 and mTOR PELP1 participates in E2-mediated cell proliferation and is a substrate of CDK4/cyclin D1, CDK2/cyclin E and CDK2/cyclin A complexes. Studies using TG mice model suggested the existence of an autocrine loop involving the CDK–cyclin D1–PELP1 axis in promoting mammary tumorigenesis PELP1 has a histone binding domain; functions as a reader of histone modifications, interacts with epigenetic modifiers such as HDAC2, KDM1, PRMT6, CARM1; and facilitates activation of genes involved in proliferation and cancer progression. PELP1 modulates the expression of miRs, PELP1-mediated epigenetic changes play important role in the regulation miR expression and many of PELP1 mediated miRS are involved in promoting metastasis. PELP1 is needed for optimal DNA damage response, is phosphorylated by DDR kinases and is important for p53 coactivation function. PELP1 also interacts with MTp53, regulates its recruitment, and alters MTp53 target gene expression. PELP1 depletion contributes to increased stability of E2F1. PELP1 binds RNA, and participates in RNA splicing. The PELP1-regulated genome includes several uniquely spliced isoforms. Mechanistic studies showed that PELP1 interaction with the arginine methyltransferase PRMT6 plays a role in RNA splicing. PELP1 plays critical roles in 60S ribosomal subunit synthesis and ribosomal RNA transcription. The SENP3-associated complex comprising PELP1, TEX10 and WDR18 is involved in maturation and nucleolar release of the large ribosomal subunit. SUMO conjugation/deconjugation of PELP1 controls its dynamic association with the AAA ATPase MDN1, a key factor of pre-60S remodeling. Modification of PELP1 promotes the recruitment of MDN1 to pre-60S particles, while deSUMOylation is needed to release both MDN1 and PELP1 from pre-ribosomes. PELP1 is widely expressed in many regions of brain, including the hippocampus, hypothalamus, and cerebral cortex. PELP1 interacts with ESR1, Src, PI3K and GSK3β in the brain. It is essential for E2-mediated extra-nuclear signaling following global cerebral ischemic. PELP1 plays an essential role in E2-mediated rapid extranuclear signaling, neuroprotection, and cognitive function in the brain. Ability of E2 to exert anti-inflammatory effects was lost in PELP1 forebrain-specific knockout mice, indicating a key role for PELP1 in E2 anti-inflammatory signaling. PELP1 is a proto-oncogene that provides cancer cells with a distinct growth and survival advantage. PELP1 interacts with various enzymes that modulate the cytoskeleton, cell migration, and metastasis. PELP1 deregulation in vivo promotes development of mammary gland hyperplasia and carcinoma PELP1 is implicated in progression of breast, endometrial, ovarian, salivary prostate, lung, pancreas, and colon neoplasms. PELP1 signaling contributes to hormonal therapy resistance. Altered localization of PLP1 contributes to tamoxifen resistance via excessive activation of the AKT pathway and cytoplasmic PELP1 induces signaling pathways that converge on ERRγ to promote cell survival in the presence of tamoxifen. AR, PELP1 and Src form constitutive complexes in prostate neoplasms model cells that exhibit androgen independence. Cytoplasmic localization of PELP1 upregulates pro-tumorigenic IKKε and secrete inflammatory signals, which through paracrine macrophage activation, regulate the migratory phenotype associated with breast cancer initiation.

… excerpt ends here. Continue reading the full article.

Illustrations

Worked examples

Example 1 — a first encounter with PELP-1

Start with the simplest possible case. Write down what PELP-1 claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to PELP-1 before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about PELP-1 ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of PELP-1

In research: PELP-1 appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses PELP-1 in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: PELP-1 is common in secondary-school and first-year university syllabi. It links to neighbouring topics Gene expression, Genes on human chromosome 17, Transcription coregulators, so understanding it makes those chapters shorter.
In everyday life: Look for PELP-1 outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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How to study PELP-1 in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what PELP-1 means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain PELP-1 out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is PELP-1 in simple terms?

Why does PELP-1 matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study PELP-1?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on PELP-1.