WBR0637

Author	[[PageAuthor::Yazan Daaboul, M.D. (Reviewed by Yazan Daaboul, M.D.)]]
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 that 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 ultraviolet B (UVB), while the other, Plate B, was kept in a dark incubator. While examining Plate A under the microscope, the researcher notices marked atypia at all levels of the epidermis with formation of 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 is 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 observed in Plate A.
Answer D	AnswerD::Hypophosphorylated Rb protein
Answer D Explanation	AnswerDExp::Hypophosphorylated Rb protein is responsible for inhibiting G1-to-S progression and subsequent 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 to maintain the hypophosphorylated and active form.
Right Answer	RightAnswer::C
Explanation	[[Explanation::The retinoblastoma RB gene product, Rb, is a protein responsible in part for maintaining cells in G1 and inhibiting G1-to-S progression. For the retinoblastoma protein to be active, however, it needs to be in the hypophosphorylated form. Hyperphosphorylation of the retinoblastoma protein by cyclin-dependent kinases (CDKs) renders it inactive, favoring to G1-to-S progression. An inactive Rb protein can also lead to the development of uncontrolled cellular proliferation. Many factors can result in retinoblastoma hyperphosphorylation, the most common of which is UV radiation. This is in part the mechanism for squamous cell carcinoma, which is characterized by marked atypia at all levels of the epidermis with formation of keratin pearls, and prominent intercellular bridges. Educational Objective: The Rb protein is a modulator of the cell cycle required to inhibit G1-to-S progression. Hyperphosphorylation of the Rb protein renders it inactive. References: Buchkovich K, Duffy LA, Harlow E. The retinoblastoma protein is phosphorylated during specific phases of the cell cycle. Cell. 1989;58(6):1097-105.]]
Approved	Approved::Yes
Keyword	WBRKeyword::Retinoblastoma, WBRKeyword::Phosphorylation, WBRKeyword::Hyperphosphorylation, WBRKeyword::Hypophosphorylation, WBRKeyword::Keratin pearls, WBRKeyword::Atypia, WBRKeyword::UVB, WBRKeyword::Squamous cell carcinoma
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