Biomedical subjects

J P Hanley

Publications and source records attributed to J P Hanley.

5 recordsLinked to original sources

PubMed1992

The carboxyl terminus of RAP30 is similar in sequence to region 4 of bacterial sigma factors and is required for function.

Transcription factor beta gamma (RAP30/74) from rat liver was previously shown in biochemical studies to control the binding of RNA polymerase II to promoters by a mechanism analogous to that utilized by bacterial sigma factors, by decreasing the affinity of polymerase for nonpromoter sites on DNA and by increasing the affinity of the enzyme for the preinitiation complex (Conaway, R. C., Garrett, K. P., Hanley, J. P., and Conaway, J. W. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 6205-6209). By constructing and analyzing mutants of beta gamma, we have identified a novel functional domain located in the carboxyl terminus of the gamma (RAP30) subunit. This domain shares sequence similarity with region 4 of bacterial sigma factors; in particular, it exhibits striking similarity to the carboxyl-terminal regions 4.1 and 4.2 of SpoIIIC (Bacillus subtilis sigma k). Evidence from biochemical studies argues that a mutant gamma (RAP30), lacking amino acid sequences similar to sigma homology region 4.2, is able to assemble with the beta (RAP74) subunit to form a mutant beta gamma (RAP30/74) with impaired ability to interact with RNA polymerase II.

Amino Acid Sequence↗

PubMed1991

Mechanism of promoter selection by RNA polymerase II: mammalian transcription factors alpha and beta gamma promote entry of polymerase into the preinitiation complex.

Productive binding of RNA polymerase II at the core region of TATA box-containing promoters is controlled by the action of the TATA factor and four additional transcription factors, designated alpha, beta gamma, delta, and epsilon, which have each been purified to near homogeneity from rat liver. This process is accomplished in three distinguishable stages. In the first stage (initial complex formation), the core promoter is packaged with the TATA factor into a binary complex that serves as the recognition site for RNA polymerase II. Here we show that, in the second stage (site selection), transcription factors alpha and beta gamma act in combination to promote selective binding of RNA polymerase II to the initial complex. Several lines of evidence argue that alpha and beta gamma function at this stage by a mechanism related to that utilized by bacterial sigma factors. In the third stage, transcription factors delta and epsilon promote assembly of the functional preinitiation complex. Our evidence supports the model that delta and epsilon enter the preinitiation complex and direct formation of stable protein-DNA contacts that anchor the transcription apparatus to the core promoter at sequences near the cap site.

Animals↗

PubMed1991

Transcription initiated by RNA polymerase II and transcription factors from liver. Structure and action of transcription factors epsilon and tau.

We have fractionated rat liver and identified a set of transcription factors that are essential for accurate initiation by RNA polymerase II. These factors were resolved into five distinct enzyme fractions designated alpha, beta gamma, delta, epsilon, and tau. Four of these fractions can now be replaced with purified proteins. alpha and beta gamma were previously purified to apparent homogeneity (Conaway, J. W., and Conaway, R. C. (1989) J. Biol. Chem. 264, 2357-2362). Here, we report purification to near homogeneity of transcription factor epsilon. Epsilon has a native molecular mass of approximately 90 kDa and is composed of 34- and 58-kDa polypeptides. Both the 34- and 58-kDa polypeptides are required for runoff transcription. In addition, we show that transcription factor tau is a rat liver homologue of the TATA factor (TFIID or BTF1) that can be efficiently replaced in transcription in vitro by recombinant yeast TFIID. Comparison of the two factors reveals, however, that they differ significantly in their abilities to direct the transcription system to discriminate between promoters of different sequences.

Animals↗

PubMed1991

Bicycle safety. What's new in '92?

There are over 100 million bicycle riders in America, according to the National Safety Council, and in the last two years more than 1.25 million accidents have been reported. About 77% of these accidents occurred among children under 15 years old. Nearly 44% of reportable injuries were in the 5-14 year old age group and 30% occurred among children under five years of age, according to the National Center for Health Statistics.

Accidents, Traffic↗

PubMed1979

Togetherness.

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Humans↗