Devita, Hellman, and Rosenberg's Cancer

LWBK1006-01 LWW-Govindan-Review November 24, 2011 11:17

16 DeVita, Hellman, and Rosenberg’s CANCER: Principles and Practice of Oncology Review

in response to the state of GTP or GDP binding. Binding of GTP induces a

conformational switch that leads to increased activity. Hydrolysis of GTP

to GDP leads to inactivation. All such proteins are lipid modified, which

allows membrane association that is important to its downstream path-

way activation. Heterotrimeric GTP-binding proteins are divided into

classes based on function; two of the classes are Gas and Gai, which

stimulate and inhibit adenylate cyclase, respectively.

Answer 1.36. The answer is A.

Phospholipase C proteins cleave PtdIns 4.5-P 2 to generate inositol-1,4,

5-triphosphate IP3 and diacylglycerol.Protein kinase A is the primary

target for cAMP. Binding of cAMP to protein kinase A leads to the acti-

vation of the protein kinase A catalytic unit through dissociation from

the regulatory unit.

Answer 1.37. The answer is D.

Myriads of cellular functions are dependent on protein–protein interac-

tions and the concentration levels of those proteins. A single stimulus

received by a cell can affect the transcription levels of hundreds of genes.

Regulation of histone deacetylases, histone acetylases, nuclear receptors,

and phosphorylation levels all play a role. Translation of protein from

mRNA can be affected by ribosomal processing. Ubiquitination results

in proteasome degradation of proteins. Lysosomes contribute to protein

degradation, often after receptors are endocytosed.

Answer 1.38. The answer is B.

Colocalization of proteins plays an important role in signal transduction

and cell signaling pathways. Ras is a GTP-binding protein that requires

the addition of a lipid moiety (generally a farnesyl group) to localize it

to the membrane. There, it interacts with and activates Raf, which then

interacts with MEK. Increased cell proliferation is one of the effects of

signaling via this pathway, so a lack of the lipid moiety could lead to

decreased cell proliferation because it is not in close proximity to the

membrane and Raf. Colocalization is an important phenomenon in cell

signaling and can also be achieved via protein–protein interactions (i.e.,

nuclear transport) and membrane localization lipid rafts.