WBR0637

Author	[[PageAuthor::Rim Halaby, M.D. [1]]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Biochemistry
Sub Category	SubCategory::Dermatology, SubCategory::Oncology
Prompt	[[Prompt::A researcher is examining 2 plates of humanized epithelial cell cultures his lab-mate had prepared in an experiment. One of the cell cultures, labeled Plate A, received 2 hours of exposure to 250 Jm2 of UVB, while the other, Plate B, was kept in a dark incubator. While examining Plate A under the microscope, he notices marked atypia at all levels of the epidermis with several keratin pearls, and prominent intercellular bridges. If the researcher is to examine the retinoblastoma protein extracted from cells in Plate A, what will his observation be?]]
Answer A	AnswerA::Hypermethylated Rb protein
Answer A Explanation	AnswerAExp::The retinoblastoma gene can be hypermethylated to inhibit its transcription; however the protein product is not methylated.
Answer B	AnswerB::Hypomethylated Rb protein
Answer B Explanation	AnswerBExp::The retinoblastoma gene can be hypomethylated to facilitate its transcription; but the gene product is generally not controlled by methylation.
Answer C	AnswerC::Hyperphosphorylated Rb protein
Answer C Explanation	AnswerCExp::Hyperphosphorylation of the Rb protein renders it inactive and allows the progression into neoplasia as seen in Plate A.
Answer D	AnswerD::Hypophosphorylated Rb protein
Answer D Explanation	AnswerDExp::Hypophosphorylated Rb protein is highly active in inhibiting G1-to-S progression and carcinogenesis.
Answer E	AnswerE::Hyperacetylated Rb protein
Answer E Explanation	AnswerEExp::Acetylation is another form of Rb control. It usually hinders the phosphorylation of pRb by cyclin-dependent kinases maintaining the hypophosphorylated and active form.
Right Answer	RightAnswer::C
Explanation	[[Explanation::The retinoblastoma gene product is a protein responsible in part for maintaining cells in G1 and inhibiting G1-to-S progression. For the retinoblastoma protein to be active it needs to be in the hypophosphorylated form. Hyperphosphorylation of the retinoblastoma protein by cyclin-dependent kinases (CDKs) renders it inactive and favoring to G1-to-S progression. An inactive Rb protein can also lead to uncontrolled cellular proliferation. Many factors can lead to retinoblastoma hyperphosphorylation the most common of which is UV radiation. This is in part the basis behind squamous cell carcinoma whose characteristic pathological findings are described in the question. Learning objective: The Rb protein is a modulator of the cell cycle required to inhibit G1-to-S progression. Its hyperphosphorylation renders it inactive. Reference: Buchkovich K, Duffy LA, Harlow E. The retinoblastoma protein is phosphorylated during specific phases of the cell cycle. Cell. 1989;58(6):1097-105. Educational Objective: References: ]]
Approved	Approved::No
Keyword	WBRKeyword::retinoblastoma, WBRKeyword::phosphorylation, WBRKeyword::hyperphosphorylation, WBRKeyword::hypophosphorylation, WBRKeyword::keratin, WBRKeyword::pearls, WBRKeyword::pearl, WBRKeyword::epithelial, WBRKeyword::plate, WBRKeyword::atypia
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